HAEM5:Burkitt lymphoma: Difference between revisions - Compendium of Cancer Genome Aberrations

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st-HAART eras~~\n\n~~[[Category:HAEM5]]\n[[Category:DISEASE]]\n[[Category:Diseases B]]~~"}}}~~

[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Burkitt Lymphoma]].

}}</blockquote>

(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ HUGO-approved gene names and symbols] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see [[Author_Instructions]] and [[Frequently Asked Questions (FAQs)|FAQs]] as well as contact your [[Leadership|Associate Editor]] or [mailto:CCGA@cancergenomics.org Technical Support].)

==Primary Author(s)*==

Becky Leung, MBBS (Hons), BSc, Pathology Queensland

==WHO Classification of Disease==

{| class="wikitable"

!Structure

!Disease

|-

|Book

|Haematolymphoid Tumours (5th ed.)

|-

|Category

|B-cell lymphoid proliferations and lymphomas

|-

|Family

|Mature B-cell neoplasms

|-

|Type

|N/A

|-

|Subtype(s)

|Burkitt lymphoma

|}

==Related Terminology==

{| class="wikitable"

|+

|Acceptable

|N/A

|-

|Not Recommended

|Burkitt cell leukaemia; atypical Burkitt lymphoma; Burkitt-like lymphoma

|}

==Gene Rearrangements==

Put your text here and fill in the table (''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')

{| class="wikitable sortable"

|-

!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)

!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|-

|EXAMPLE: ''ABL1''||EXAMPLE: ''BCR::ABL1''||EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||EXAMPLE: t(9;22)(q34;q11.2)

|EXAMPLE: Common (CML)

|EXAMPLE: D, P, T

|EXAMPLE: Yes (WHO, NCCN)

|EXAMPLE:

The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).

|-

|EXAMPLE: ''CIC''

|EXAMPLE: ''CIC::DUX4''

|EXAMPLE: Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.

|EXAMPLE: t(4;19)(q25;q13)

|EXAMPLE: Common (CIC-rearranged sarcoma)

|EXAMPLE: D

|

|EXAMPLE:

''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).

|-

|EXAMPLE: ''ALK''

|EXAMPLE: ''ELM4::ALK''

Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''

|EXAMPLE: Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.

|EXAMPLE: N/A

|EXAMPLE: Rare (Lung adenocarcinoma)

|EXAMPLE: T

|

|EXAMPLE:

Both balanced and unbalanced forms are observed by FISH (add references).

|-

|EXAMPLE: ''ABL1''

|EXAMPLE: N/A

|EXAMPLE: Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.

|EXAMPLE: N/A

|EXAMPLE: Recurrent (IDH-wildtype Glioblastoma)

|EXAMPLE: D, P, T

|

|-

|

|}

<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>

The development of Burkitt lymphoma is dependent on the constitutive expression of the ''MYC'' proto-oncogene. The MYC encoded protein is a transcriptional regulator, controlling target genes involved in cell cycle regulation, metabolism and apoptosis. Dysregulation of ''MYC'' expression occurs due to juxtaposition of regulatory elements of the immunoglobulin loci, usually ''IGH'', but also ''IGL'' or ''IGK''. Overexpression of ''MYC'' correlates with increased cell survival. The different Burkitt lymphoma subtypes harbour diverse ''MYC'' and ''IGH'' locus breakpoints. In endemic Burkitt lymphoma, ''MYC'' usually breaks several hundred kilobases further upstream and ''IG'' usually breaks in the VDJ region. In contrast, most sporadic and immunodeficiency-associated Burkitt lymphoma have chromosomal breakpoints within exon 1 and the first intron of ''MYC'' and at the class switch region of ''IG''<ref>{{Cite journal|last=Neri|first=A.|last2=Barriga|first2=F.|last3=Knowles|first3=D. M.|last4=Magrath|first4=I. T.|last5=Dalla-Favera|first5=R.|date=1988-04-01|title=Different regions of the immunoglobulin heavy-chain locus are involved in chromosomal translocations in distinct pathogenetic forms of Burkitt lymphoma.|url=http://dx.doi.org/10.1073/pnas.85.8.2748|journal=Proceedings of the National Academy of Sciences|volume=85|issue=8|pages=2748–2752|doi=10.1073/pnas.85.8.2748|issn=0027-8424}}</ref>. Although fluorescence ''in situ'' hydribisation (FISH) methods are well established in most pathology laboratories, no single probe set is able to cover all ''MYC'' breakpoints. In particular, distant breakpoints, complex rearrangements and cryptic insertions may be overlooked<ref>{{Cite journal|last=Muñoz-Mármol|first=Ana M|last2=Sanz|first2=Carolina|last3=Tapia|first3=Gustavo|last4=Marginet|first4=Ruth|last5=Ariza|first5=Aurelio|last6=Mate|first6=José L|date=2013-09|title=MYC status determination in aggressive B-cell lymphoma: the impact of FISH probe selection|url=http://doi.wiley.com/10.1111/his.12178|journal=Histopathology|language=en|volume=63|issue=3|pages=418–424|doi=10.1111/his.12178}}</ref>. Hence, multiple FISH probe sets are required for comprehensive detection of clinically relevant ''MYC'' gene rearrangements.

A translocation involving ''MYC'' cannot be detected by FISH or classical cytogenetics in a small percentage of cases (less than 5%). This may be due to technical issues, such as a very small excision of ''MYC'' and insertion of the gene onto the ''IG'' loci, or a breakpoint localised outside the regions covered by the utilised FISH probes<ref>{{Cite journal|last=De Falco|first=Giulia|last2=Ambrosio|first2=Maria Raffaella|last3=Fuligni|first3=Fabio|last4=Onnis|first4=Anna|last5=Bellan|first5=Cristiana|last6=Rocca|first6=Bruno Jim|last7=Navari|first7=Mohsen|last8=Etebari|first8=Maryam|last9=Mundo|first9=Lucia|date=2015-10-09|title=Burkitt lymphoma beyond MYC translocation: N-MYC and DNA methyltransferases dysregulation|url=http://dx.doi.org/10.1186/s12885-015-1661-7|journal=BMC Cancer|volume=15|issue=1|doi=10.1186/s12885-015-1661-7|issn=1471-2407}}</ref>. Mechanisms other then translocation that similarly lead to ''MYC'' overexpression have also been implicated in the development of Burkitt lymphoma<ref>{{Cite journal|last=Leucci|first=E|last2=Cocco|first2=M|last3=Onnis|first3=A|last4=De Falco|first4=G|last5=van Cleef|first5=P|last6=Bellan|first6=C|last7=van Rijk|first7=A|last8=Nyagol|first8=J|last9=Byakika|first9=B|date=2008-09-18|title=MYC

translocation‐negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation|url=http://dx.doi.org/10.1002/path.2410|journal=The Journal of Pathology|volume=216|issue=4|pages=440–450|doi=10.1002/path.2410|issn=0022-3417}}</ref>. Investigation for these should be considered in the presence of a consistent clinical and laboratory phenotype, where fusions are not detected.

{| class="wikitable sortable"

|-

!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence

|-

|t(8;14)(q24;q32)||5'<nowiki/>''IGH'' / 3MYC''||der(14)||85%

|-

|t(8;22)(q24;q11)

|5'<nowiki/>''MYC'' / 3IGL''

|der(8)

|10%

|-

|t(2;8)(p12;q24)||5'<nowiki/>''MYC'' / 3IGK''||der(8)||5%

|}

<center>'''End of V4 Section'''

----

</blockquote>

<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:

* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

* Gene Mutations (SNV/INDEL)}}</blockquote>

Deciphering the genomic landscape of Burkitt lymphoma provides additional molecular targets for new treatment regimens. Burkitt lymphoma is often curable using intensive chemotherapy treatments. However, these regimens may not be well tolerated by older individuals and further treatment options are required for those who exhibit refractory or relapsed disease.

Considerations are for inhibitors of PI3K signaling and downstream pathways, and inhibiting cyclin dependent kinase 4/6 to block cyclin D3 mediated cell cycle progression.

<center>'''End of V4 Section'''

----

</blockquote>

==Individual Region Genomic Gain/Loss/LOH==

Put your text here and fill in the table (''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'')

{| class="wikitable sortable"

|-

!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|-

|EXAMPLE:

7

|EXAMPLE: Loss

|EXAMPLE:

chr7

|EXAMPLE:

Unknown

|EXAMPLE: D, P

|EXAMPLE: No

|EXAMPLE:

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).

|-

|EXAMPLE:

8

|EXAMPLE: Gain

|EXAMPLE:

chr8

|EXAMPLE:

Unknown

|EXAMPLE: D, P

|

|EXAMPLE:

Common recurrent secondary finding for t(8;21) (add references).

|-

|EXAMPLE:

17

|EXAMPLE: Amp

|EXAMPLE:

17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]

|EXAMPLE:

''ERBB2''

|EXAMPLE: D, P, T

|

|EXAMPLE:

Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.

|-

|

|}

<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>

Most often, Burkitt lymphoma is associated with a simple karyotype. However additional chromosomal abnormalities may also occur and play a role in disease progression, see the table below for the more commonly implicated cytogenetic abnormalities.

In the context of a Burkitt lymphoma-like phenotype and/or Burkitt-like morphological appearance, the diagnosis of 'Burkitt-like lymphoma with 11q aberration' should be considered. This provisional WHO entity lacks a detectable ''MYC'' rearrangement, but shows alterations of 11q. These 11q alterations typically include proximal gains (eg 11q23.2-23.3), and telomeric losses (eg 11q24.1-ter). MicroRNA and gene expression profiling patterns are consistent with Burkitt lymphoma. Other common karyotypic features of this condition include a complex karyotype, and lack of the 1q loss typical of Burkitt lymphoma.

{| class="wikitable sortable"

|-

!Chromosome Number!!Gain/Loss/Amp/LOH!!Region

|-

|1q||Gain||21-25

|-

|6q

|Loss

|11-14

|-

|7||Gain||

|-

|8

|Gain

|

|-

|12

|Gain

|

|-

|13q

|Loss

|32-34

|-

|17p

|Loss

|

|-

|18

|Gain

|

|}

<center>'''End of V4 Section'''

----

</blockquote>

==Characteristic Chromosomal or Other Global Mutational Patterns==

Put your text here and fill in the table (I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')

{| class="wikitable sortable"

|-

!Chromosomal Pattern

!Molecular Pathogenesis

!Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|-

|EXAMPLE:

Co-deletion of 1p and 18q

|EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

|EXAMPLE: Common (Oligodendroglioma)

|EXAMPLE: D, P

|

|-

|EXAMPLE:

Microsatellite instability - hypermutated

|

|EXAMPLE: Common (Endometrial carcinoma)

|EXAMPLE: P, T

|

|-

|

|}

==Gene Mutations (SNV/INDEL)==

Put your text here and fill in the table (''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')

{| class="wikitable sortable"

|-

!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|-

|EXAMPLE:''EGFR''

|EXAMPLE: Exon 18-21 activating mutations

|EXAMPLE: Oncogene

|EXAMPLE: Common (lung cancer)

|EXAMPLE: T

|EXAMPLE: Yes (NCCN)

|EXAMPLE: Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).

|-

|EXAMPLE: ''TP53''; Variable LOF mutations

|EXAMPLE: Variable LOF mutations

|EXAMPLE: Tumor Supressor Gene

|EXAMPLE: Common (breast cancer)

|EXAMPLE: P

|

|EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.

|-

|EXAMPLE: ''BRAF''; Activating mutations

|EXAMPLE: Activating mutations

|EXAMPLE: Oncogene

|EXAMPLE: Common (melanoma)

|EXAMPLE: T

|

|-

|

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ cBioportal], [https://cancer.sanger.ac.uk/cosmic COSMIC], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>

{| class="wikitable sortable"

|-

!Gene!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)

|-

|''MYC''||Oncogene||GOF||67%

|-

|''ID3<ref>{{Cite journal|last=Richter|first=Julia|last2=Schlesner|first2=Matthias|last3=Hoffmann|first3=Steve|last4=Kreuz|first4=Markus|last5=Leich|first5=Ellen|last6=Burkhardt|first6=Birgit|last7=Rosolowski|first7=Maciej|last8=Ammerpohl|first8=Ole|last9=Wagener|first9=Rabea|date=2012-12|title=Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing|url=https://pubmed.ncbi.nlm.nih.gov/23143595|journal=Nature Genetics|volume=44|issue=12|pages=1316–1320|doi=10.1038/ng.2469|issn=1546-1718|pmid=23143595}}</ref>''

|Tumour suppressor

|LOF

|34%

|-

|''DDX3X<ref>{{Cite journal|last=Mo|first=Jie|last2=Liang|first2=Huifang|last3=Su|first3=Chen|last4=Li|first4=Pengcheng|last5=Chen|first5=Jin|last6=Zhang|first6=Bixiang|date=2021-02-24|title=DDX3X: structure, physiologic functions and cancer|url=http://dx.doi.org/10.1186/s12943-021-01325-7|journal=Molecular Cancer|volume=20|issue=1|doi=10.1186/s12943-021-01325-7|issn=1476-4598}}</ref>''

|Tumour suppressor

|LOF

|34%

|-

|''BCL6<ref>{{Cite journal|last=Kl|first=Bunting|last2=Am|first2=Melnick|date=2013 Jun|title=New effector functions and regulatory mechanisms of BCL6 in normal and malignant lymphocytes|url=https://pubmed.ncbi.nlm.nih.gov/23725655/|language=en|doi=10.1016/j.coi.2013.05.003|pmc=PMC4075446|pmid=23725655}}</ref>''

|Oncogene

|GOF

|25%

|-

|''BCL7A<ref>{{Cite journal|last=Zani|first=V. J.|last2=Asou|first2=N.|last3=Jadayel|first3=D.|last4=Heward|first4=J. M.|last5=Shipley|first5=J.|last6=Nacheva|first6=E.|last7=Takasuki|first7=K.|last8=Catovsky|first8=D.|last9=Dyer|first9=M. J.|date=1996-04-15|title=Molecular cloning of complex chromosomal translocation t(8;14;12)(q24.1;q32.3;q24.1) in a Burkitt lymphoma cell line defines a new gene (BCL7A) with homology to caldesmon|url=https://pubmed.ncbi.nlm.nih.gov/8605326|journal=Blood|volume=87|issue=8|pages=3124–3134|issn=0006-4971|pmid=8605326}}</ref>''

|Oncogene

|GOF

|24%

|-

|''FBXO11<ref>{{Cite journal|last=Pighi|first=Chiara|last2=Compagno|first2=Mara|last3=Wang|first3=Qi|last4=Cheong|first4=Taek-Chin|last5=Poggio|first5=Teresa|last6=Langellotto|first6=Fernanda|last7=Francia di Celle|first7=Paola|last8=Zamò|first8=Alberto|last9=Chiarle|first9=Roberto|date=2015-12-03|title=FBXO11, a Regulator of BCL6 Stability, Is Recurrently Mutated in Burkitt Lymphoma|url=http://dx.doi.org/10.1182/blood.v126.23.3673.3673|journal=Blood|volume=126|issue=23|pages=3673–3673|doi=10.1182/blood.v126.23.3673.3673|issn=0006-4971}}</ref>''

|Tumour suppressor

|LOF

|23%

|-

|''FOXO1<ref>{{Cite journal|last=Zhou|first=Peixun|last2=Blain|first2=Alex E.|last3=Newman|first3=Alexander M.|last4=Zaka|first4=Masood|last5=Chagaluka|first5=George|last6=Adlar|first6=Filbert R.|last7=Offor|first7=Ugonna T.|last8=Broadbent|first8=Casey|last9=Chaytor|first9=Lewis|date=2019-07-23|title=Sporadic and endemic Burkitt lymphoma have frequent FOXO1 mutations but distinct hotspots in the AKT recognition motif|url=https://pubmed.ncbi.nlm.nih.gov/31300419|journal=Blood Advances|volume=3|issue=14|pages=2118–2127|doi=10.1182/bloodadvances.2018029546|issn=2473-9537|pmc=6650741|pmid=31300419}}</ref>''

|Oncogene

|GOF

|23%

|-

|''SMARCA4<ref>{{Cite journal|last=Love|first=Cassandra|last2=Sun|first2=Zhen|last3=Jima|first3=Dereje|last4=Li|first4=Guojie|last5=Zhang|first5=Jenny|last6=Miles|first6=Rodney|last7=Richards|first7=Kristy L.|last8=Dunphy|first8=Cherie H.|last9=Choi|first9=William W. L.|date=2012-12|title=The genetic landscape of mutations in Burkitt lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/23143597|journal=Nature Genetics|volume=44|issue=12|pages=1321–1325|doi=10.1038/ng.2468|issn=1546-1718|pmc=3674561|pmid=23143597}}</ref>''

|Tumour suppressor

|LOF

|23%

|-

|''ARID1A<ref>{{Cite journal|last=Love|first=Cassandra|last2=Sun|first2=Zhen|last3=Jima|first3=Dereje|last4=Li|first4=Guojie|last5=Zhang|first5=Jenny|last6=Miles|first6=Rodney|last7=Richards|first7=Kristy L.|last8=Dunphy|first8=Cherie H.|last9=Choi|first9=William W. L.|date=2012-12|title=The genetic landscape of mutations in Burkitt lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/23143597|journal=Nature Genetics|volume=44|issue=12|pages=1321–1325|doi=10.1038/ng.2468|issn=1546-1718|pmc=3674561|pmid=23143597}}</ref>''

|Tumour suppressor

|LOF

|18%

|-

|''TP53<ref>{{Cite journal|last=Shannon-Lowe|first=Claire|last2=Rickinson|first2=Alan B.|last3=Bell|first3=Andrew I.|date=2017-10-19|title=Epstein-Barr virus-associated lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/28893938|journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences|volume=372|issue=1732|doi=10.1098/rstb.2016.0271|issn=1471-2970|pmc=5597738|pmid=28893938}}</ref>''

|Tumour suppressor

|LOF

|17%

|-

|''CTCF<ref>{{Cite journal|last=Chau|first=Charles M.|last2=Zhang|first2=Xiao-Yong|last3=McMahon|first3=Steven B.|last4=Lieberman|first4=Paul M.|date=2006-06-15|title=Regulation of Epstein-Barr Virus Latency Type by the Chromatin Boundary Factor CTCF|url=https://jvi.asm.org/content/80/12/5723|journal=Journal of Virology|language=en|volume=80|issue=12|pages=5723–5732|doi=10.1128/JVI.00025-06|issn=0022-538X|pmc=PMC1472585|pmid=16731911}}</ref>''

|Tumour suppressor

|LOF

|16%

|-

|''CREBBP<ref>{{Cite journal|last=Love|first=Cassandra|last2=Sun|first2=Zhen|last3=Jima|first3=Dereje|last4=Li|first4=Guojie|last5=Zhang|first5=Jenny|last6=Miles|first6=Rodney|last7=Richards|first7=Kristy L.|last8=Dunphy|first8=Cherie H.|last9=Choi|first9=William W. L.|date=2012-12|title=The genetic landscape of mutations in Burkitt lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/23143597|journal=Nature Genetics|volume=44|issue=12|pages=1321–1325|doi=10.1038/ng.2468|issn=1546-1718|pmc=3674561|pmid=23143597}}</ref>''

|Tumour suppressor

|LOF

|15%

|-

|''TCL1A<ref>{{Cite journal|last=Aggarwal|first=Mohit|last2=Villuendas|first2=Raquel|last3=Gomez|first3=Gonzalo|last4=Rodriguez-Pinilla|first4=Socorro M|last5=Sanchez-Beato|first5=Margarita|last6=Alvarez|first6=David|last7=Martinez|first7=Nerea|last8=Rodriguez|first8=Antonia|last9=Castillo|first9=Maria E|date=2008-09-26|title=TCL1A expression delineates biological and clinical variability in B-cell lymphoma|url=http://dx.doi.org/10.1038/modpathol.2008.148|journal=Modern Pathology|volume=22|issue=2|pages=206–215|doi=10.1038/modpathol.2008.148|issn=0893-3952}}</ref>''

|Oncogene

|GOF

|15%

|-

|''BCR<ref>{{Cite journal|last=Küppers|first=Ralf|date=2005-04|title=Mechanisms of B-cell lymphoma pathogenesis|url=http://dx.doi.org/10.1038/nrc1589|journal=Nature Reviews Cancer|volume=5|issue=4|pages=251–262|doi=10.1038/nrc1589|issn=1474-175X}}</ref>''

|Oncogene

|GOF

|15%

|-

|''TCF3<ref>{{Cite journal|last=Schmitz|first=Roland|last2=Young|first2=Ryan M.|last3=Ceribelli|first3=Michele|last4=Jhavar|first4=Sameer|last5=Xiao|first5=Wenming|last6=Zhang|first6=Meili|last7=Wright|first7=George|last8=Shaffer|first8=Arthur L.|last9=Hodson|first9=Daniel J.|date=2012-10-04|title=Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics|url=https://pubmed.ncbi.nlm.nih.gov/22885699|journal=Nature|volume=490|issue=7418|pages=116–120|doi=10.1038/nature11378|issn=1476-4687|pmc=3609867|pmid=22885699}}</ref>''

|Oncogene

|GOF

|14%

|-

|''CCND3<ref>{{Cite journal|last=Schmitz|first=Roland|last2=Young|first2=Ryan M.|last3=Ceribelli|first3=Michele|last4=Jhavar|first4=Sameer|last5=Xiao|first5=Wenming|last6=Zhang|first6=Meili|last7=Wright|first7=George|last8=Shaffer|first8=Arthur L.|last9=Hodson|first9=Daniel J.|date=2012-10-04|title=Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics|url=https://pubmed.ncbi.nlm.nih.gov/22885699|journal=Nature|volume=490|issue=7418|pages=116–120|doi=10.1038/nature11378|issn=1476-4687|pmc=3609867|pmid=22885699}}</ref>''

|Oncogene

|GOF

|14%

|}

<center>'''End of V4 Section'''

----

</blockquote>

==Epigenomic Alterations==

Put your text here

==Genes and Main Pathways Involved==

Put your text here and fill in the table (''Instructions: Please include references throughout the table. Do not delete the table.)''

{| class="wikitable sortable"

|-

!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

|-

|EXAMPLE: ''BRAF'' and ''MAP2K1''; Activating mutations

|EXAMPLE: MAPK signaling

|EXAMPLE: Increased cell growth and proliferation

|-

|EXAMPLE: ''CDKN2A''; Inactivating mutations

|EXAMPLE: Cell cycle regulation

|EXAMPLE: Unregulated cell division

|-

|EXAMPLE: ''KMT2C'' and ''ARID1A''; Inactivating mutations

|EXAMPLE: Histone modification, chromatin remodeling

|EXAMPLE: Abnormal gene expression program

|-

|

|}

<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>

''MYC'' is the most commonly mutated gene in Burkitt lymphoma, such variants lead to constitutive expression of ''MYC'', which drives cell survival. Aberrant somatic hypermutation is understood to be the major cause of ''MYC'' breakpoint formation and the presence of hypermutation in tandem with MYC rearrangement may be detectable if using sequencing methodologies.

Localised ''TP53'' inactivating mutations or chromosomal deletions involving ''TP53'' are also common in Burkitt lymphoma, and cause abrogation of ''TP53''-dependent apoptotic pathways. Loss of ''TP53'' function through the aforementioned means, or dysregulation due to the mutation of ''TP53'' regulatory elements, is believed to be key to the development of Burkitt lymphoma<ref>{{Cite journal|last=Shannon-Lowe|first=Claire|last2=Rickinson|first2=Alan B.|last3=Bell|first3=Andrew I.|date=2017-10-19|title=Epstein-Barr virus-associated lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/28893938|journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences|volume=372|issue=1732|doi=10.1098/rstb.2016.0271|issn=1471-2970|pmc=5597738|pmid=28893938}}</ref>.

''TCF3'' or ''ID3'' mutations are seen in approximately 70% of sporadic Burkitt lymphoma. The normal function of transcription factor E2A (encoded by ''TCF3'') is regulation of the differentiation of B-cells in the germinal centre. Mutations in ''TCF3'' leads to reduced affinity for its negative regulator, ''ID3'', promoting constitutive activity. ''TCF3'' promotes B-cell receptor signaling in Burkitt lymphoma, which enhances survival via the PI3 kinase pathway. ''TCF3'' also transactivates ''CCND3'' which encodes cyclin D3 expression, promoting cell cycle progression and proliferation<ref>{{Cite journal|last=Schmitz|first=Roland|last2=Young|first2=Ryan M.|last3=Ceribelli|first3=Michele|last4=Jhavar|first4=Sameer|last5=Xiao|first5=Wenming|last6=Zhang|first6=Meili|last7=Wright|first7=George|last8=Shaffer|first8=Arthur L.|last9=Hodson|first9=Daniel J.|date=2012-10-04|title=Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics|url=https://pubmed.ncbi.nlm.nih.gov/22885699|journal=Nature|volume=490|issue=7418|pages=116–120|doi=10.1038/nature11378|issn=1476-4687|pmc=3609867|pmid=22885699}}</ref>.

Mutations overall, and in particular in ''TCF3'' and ''ID3'', are less common in endemic Burkitt lymphoma when compared to sporadic cases. It is postulated that this additional mutational burden may take the place of EBV in sporadic Burkitt lymphomagenesis, given that either mechanism can lead to the activation of B-cell receptor signaling.

The gene expression and micro-RNA expression profiles of Burkitt lymphoma are different from other lymphomas. The expression profiles of endemic and sporadic BL are also slightly different to each other. There may be grey zones where Burkitt lymphoma is difficult to distinguish from diffuse large B-cell lymphoma based on gene expression, hence expression should not be used as an independent diagnostic tool<ref>{{Cite journal|last=Shannon-Lowe|first=Claire|last2=Rickinson|first2=Alan B.|last3=Bell|first3=Andrew I.|date=2017-10-19|title=Epstein-Barr virus-associated lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/28893938|journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences|volume=372|issue=1732|doi=10.1098/rstb.2016.0271|issn=1471-2970|pmc=5597738|pmid=28893938}}</ref>.

<center>'''End of V4 Section'''

----

</blockquote>

==Genetic Diagnostic Testing Methods==

Put your text here (''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')

==Familial Forms==

The X-linked lymphoproliferative syndrome 'Duncan disease', is associated with SH2D1A mutations. Individuals with this condition are at greatly increased risk of developing Burkitt lymphoma.

==Additional Information==

Put your text here

==Links==

[[HAEM5:High grade B-cell lymphoma with 11q aberrations]]

==References==

(use the "Cite" icon at the top of the page) (''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''''.'') <references />

==Notes==

<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''Associate Editor'']] or other CCGA representative. When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

Prior Author(s):

<nowiki>*</nowiki>''Citation of this Page'': “Burkitt lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Burkitt_lymphoma</nowiki>.

==Other Sections==

Cancer Sub-Classification/Subtype

Burkitt lymphoma

Definition/Description of Disease

Burkitt lymphoma is a clinically aggressive but curable lymphoma with three aetiologically distinct subtypes, these being endemic, sporadic and immunodeficiency-associated Burkitt lymphoma. Infection with Epstein-Bar virus (EBV), also known as human herpesvirus 4, is seen all three subtypes, but is most strongly associated with endemic Burkitt Lymphoma. Detectable EBV infection is not essential for diagnosis, and may not be the cause in all cases; the frequency of EBV infection varies according to the epidemiological subtype of Burkitt lymphoma. The clinical presentation often involves extra-nodal sites but the disease can also present as an acute leukaemia.

Synonyms/Terminology

Burkitt cell leukaemia

Obsolete terms

*Burkitt tumour

*Malignant lymphoma, undifferentiated, Burkitt type

*Malignant lymphoma, small non-cleaved, Burkitt type

Epidemiology/Prevalence

Endemic Burkitt lymphoma

*Highly associated with Epstein-Barr virus (EBV genome present in >95% of neoplastic cells) and ''Plasmodium falciparum'' infection

*Occurs in equatorial Africa and Papua New Guinea, with a distribution that overlaps with regions endemic for malaria

*Demographics: peak incidence among children aged 4-7 years

*The incidence is higher in males than females, at a ratio of 2:1

Sporadic Burkitt lymphoma

*EBV detected in 20-30% of cases, proportion of EBV positive cases appears to be much higher in adults than in children

*Occurs worldwide

*Western Europe and USA: low incidence, accounting for only 1-2% of all lymphomas overall (30-50% of all childhood lymphomas)

*South America and northern Africa: incidence between that of sporadic Burkitt lymphoma in developed countries and endemic Burkitt lymphoma

*Demographics: peak incidence among children and young adults (median age 30 years, with separate incidence peak in elderly patients)

*M:F 2-3:1

Immunodeficiency-associated Burkitt lymphoma

*EBV detected in 25-40% of cases

*Associated with HIV infection (most commonly) and other forms of immunosuppression

*Occurs early in the course of HIV infection, when CD4+ T cell counts are still high

*Increased risk of developing Burkitt lymphoma has persisted across the pre-and post-HAART eras

[[Category:HAEM5]]

[[Category:DISEASE]]

[[Category:Diseases B]]

@@ Line 1: / Line 1: @@
-st-HAART eras\n\n[[Category:HAEM5]]\n[[Category:DISEASE]]\n[[Category:Diseases B]]"}}}
+{{DISPLAYTITLE:Burkitt lymphoma}}
+[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
+{{Under Construction}}
+<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Burkitt Lymphoma]].
+}}</blockquote>
+<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span>
+==Primary Author(s)*==
+Becky Leung, MBBS (Hons), BSc, Pathology Queensland
+==WHO Classification of Disease==
+{| class="wikitable"
+!Structure
+!Disease
+|-
+|Book
+|Haematolymphoid Tumours (5th ed.)
+|-
+|Category
+|B-cell lymphoid proliferations and lymphomas
+|-
+|Family
+|Mature B-cell neoplasms
+|-
+|Type
+|N/A
+|-
+|Subtype(s)
+|Burkitt lymphoma
+|}
+==Related Terminology==
+{| class="wikitable"
+|+
+|Acceptable
+|N/A
+|-
+|Not Recommended
+|Burkitt cell leukaemia; atypical Burkitt lymphoma; Burkitt-like lymphoma
+|}
+==Gene Rearrangements==
+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
+{| class="wikitable sortable"
+|-
+!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
+!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
+!Clinical Relevance Details/Other Notes
+|-
+|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
+|<span class="blue-text">EXAMPLE:</span> Common (CML)
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
+|<span class="blue-text">EXAMPLE:</span>
+The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
+|-
+|<span class="blue-text">EXAMPLE:</span> ''CIC''
+|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
+|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
+|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
+|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
+|<span class="blue-text">EXAMPLE:</span> D
+|
+|<span class="blue-text">EXAMPLE:</span>
+''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
+|-
+|<span class="blue-text">EXAMPLE:</span> ''ALK''
+|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
+Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
+|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
+|<span class="blue-text">EXAMPLE:</span> N/A
+|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
+|<span class="blue-text">EXAMPLE:</span> T
+|
+|<span class="blue-text">EXAMPLE:</span>
+Both balanced and unbalanced forms are observed by FISH (add references).
+|-
+|<span class="blue-text">EXAMPLE:</span> ''ABL1''
+|<span class="blue-text">EXAMPLE:</span> N/A
+|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
+|<span class="blue-text">EXAMPLE:</span> N/A
+|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|
+|
+|-
+|
+|
+|
+|
+|
+|
+|
+|
+|}
+<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
+The development of Burkitt lymphoma is dependent on the constitutive expression of the ''MYC'' proto-oncogene. The MYC encoded protein is a transcriptional regulator, controlling target genes involved in cell cycle regulation, metabolism and apoptosis. Dysregulation of ''MYC'' expression occurs due to juxtaposition of regulatory elements of the immunoglobulin loci, usually ''IGH'', but also ''IGL'' or ''IGK''. Overexpression of ''MYC'' correlates with increased cell survival. The different Burkitt lymphoma subtypes harbour diverse ''MYC'' and ''IGH'' locus breakpoints. In endemic Burkitt lymphoma, ''MYC'' usually breaks several hundred kilobases further upstream and ''IG'' usually breaks in the VDJ region. In contrast, most sporadic and immunodeficiency-associated Burkitt lymphoma have chromosomal breakpoints within exon 1 and the first intron of ''MYC'' and at the class switch region of ''IG''<ref>{{Cite journal|last=Neri|first=A.|last2=Barriga|first2=F.|last3=Knowles|first3=D. M.|last4=Magrath|first4=I. T.|last5=Dalla-Favera|first5=R.|date=1988-04-01|title=Different regions of the immunoglobulin heavy-chain locus are involved in chromosomal translocations in distinct pathogenetic forms of Burkitt lymphoma.|url=http://dx.doi.org/10.1073/pnas.85.8.2748|journal=Proceedings of the National Academy of Sciences|volume=85|issue=8|pages=2748–2752|doi=10.1073/pnas.85.8.2748|issn=0027-8424}}</ref>. Although fluorescence ''in situ'' hydribisation (FISH) methods are well established in most pathology laboratories, no single probe set is able to cover all ''MYC'' breakpoints. In particular, distant breakpoints, complex rearrangements and cryptic insertions may be overlooked<ref>{{Cite journal|last=Muñoz-Mármol|first=Ana M|last2=Sanz|first2=Carolina|last3=Tapia|first3=Gustavo|last4=Marginet|first4=Ruth|last5=Ariza|first5=Aurelio|last6=Mate|first6=José L|date=2013-09|title=MYC status determination in aggressive B-cell lymphoma: the impact of FISH probe selection|url=http://doi.wiley.com/10.1111/his.12178|journal=Histopathology|language=en|volume=63|issue=3|pages=418–424|doi=10.1111/his.12178}}</ref>. Hence, multiple FISH probe sets are required for comprehensive detection of clinically relevant ''MYC'' gene rearrangements.
+A translocation involving ''MYC'' cannot be detected by FISH or classical cytogenetics in a small percentage of cases (less than 5%). This may be due to technical issues, such as a very small excision of ''MYC'' and insertion of the gene onto the ''IG'' loci, or a breakpoint localised outside the regions covered by the utilised FISH probes<ref>{{Cite journal|last=De Falco|first=Giulia|last2=Ambrosio|first2=Maria Raffaella|last3=Fuligni|first3=Fabio|last4=Onnis|first4=Anna|last5=Bellan|first5=Cristiana|last6=Rocca|first6=Bruno Jim|last7=Navari|first7=Mohsen|last8=Etebari|first8=Maryam|last9=Mundo|first9=Lucia|date=2015-10-09|title=Burkitt lymphoma beyond MYC translocation: N-MYC and DNA methyltransferases dysregulation|url=http://dx.doi.org/10.1186/s12885-015-1661-7|journal=BMC Cancer|volume=15|issue=1|doi=10.1186/s12885-015-1661-7|issn=1471-2407}}</ref>. Mechanisms other then translocation that similarly lead to ''MYC'' overexpression have also been implicated in the development of Burkitt lymphoma<ref>{{Cite journal|last=Leucci|first=E|last2=Cocco|first2=M|last3=Onnis|first3=A|last4=De Falco|first4=G|last5=van Cleef|first5=P|last6=Bellan|first6=C|last7=van Rijk|first7=A|last8=Nyagol|first8=J|last9=Byakika|first9=B|date=2008-09-18|title=MYC
+            translocation‐negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation|url=http://dx.doi.org/10.1002/path.2410|journal=The Journal of Pathology|volume=216|issue=4|pages=440–450|doi=10.1002/path.2410|issn=0022-3417}}</ref>. Investigation for these should be considered in the presence of a consistent clinical and laboratory phenotype, where fusions are not detected.
+{| class="wikitable sortable"
+|-
+!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
+|-
+|t(8;14)(q24;q32)||5'<nowiki/>''IGH'' / 3MYC''||der(14)||85%
+|-
+|t(8;22)(q24;q11)
+|5'<nowiki/>''MYC'' / 3IGL''
+|der(8)
+|10%
+|-
+|t(2;8)(p12;q24)||5'<nowiki/>''MYC'' / 3IGK''||der(8)||5%
+|}
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+</blockquote>
+<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
+* Chromosomal Rearrangements (Gene Fusions)
+* Individual Region Genomic Gain/Loss/LOH
+* Characteristic Chromosomal Patterns
+* Gene Mutations (SNV/INDEL)}}</blockquote>
+Deciphering the genomic landscape of Burkitt lymphoma provides additional molecular targets for new treatment regimens. Burkitt lymphoma is often curable using intensive chemotherapy treatments. However, these regimens may not be well tolerated by older individuals and further treatment options are required for those who exhibit refractory or relapsed disease.
+Considerations are for inhibitors of PI3K signaling and downstream pathways, and inhibiting cyclin dependent kinase 4/6 to block cyclin D3 mediated cell cycle progression.
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+</blockquote>
+==Individual Region Genomic Gain/Loss/LOH==
+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
+{| class="wikitable sortable"
+|-
+!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
+!Clinical Relevance Details/Other Notes
+|-
+|<span class="blue-text">EXAMPLE:</span>
+|<span class="blue-text">EXAMPLE:</span> Loss
+|<span class="blue-text">EXAMPLE:</span>
+chr7
+|<span class="blue-text">EXAMPLE:</span>
+Unknown
+|<span class="blue-text">EXAMPLE:</span> D, P
+|<span class="blue-text">EXAMPLE:</span> No
+|<span class="blue-text">EXAMPLE:</span>
+Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
+|-
+|<span class="blue-text">EXAMPLE:</span>
+|<span class="blue-text">EXAMPLE:</span> Gain
+|<span class="blue-text">EXAMPLE:</span>
+chr8
+|<span class="blue-text">EXAMPLE:</span>
+Unknown
+|<span class="blue-text">EXAMPLE:</span> D, P
+|
+|<span class="blue-text">EXAMPLE:</span>
+Common recurrent secondary finding for t(8;21) (add references).
+|-
+|<span class="blue-text">EXAMPLE:</span>
+|<span class="blue-text">EXAMPLE:</span> Amp
+|<span class="blue-text">EXAMPLE:</span>
+q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
+|<span class="blue-text">EXAMPLE:</span>
+''ERBB2''
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|
+|<span class="blue-text">EXAMPLE:</span>
+Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
+|-
+|
+|
+|
+|
+|
+|
+|
+|}
+<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>
+Most often, Burkitt lymphoma is associated with a simple karyotype. However additional chromosomal abnormalities may also occur and play a role in disease progression, see the table below for the more commonly implicated cytogenetic abnormalities.
+In the context of a Burkitt lymphoma-like phenotype and/or Burkitt-like morphological appearance, the diagnosis of 'Burkitt-like lymphoma with 11q aberration' should be considered. This provisional WHO entity lacks a detectable ''MYC'' rearrangement, but shows alterations of 11q. These 11q alterations typically include proximal gains (eg 11q23.2-23.3), and telomeric losses (eg 11q24.1-ter). MicroRNA and gene expression profiling patterns are consistent with Burkitt lymphoma. Other common karyotypic features of this condition include a complex karyotype, and lack of the 1q loss typical of Burkitt lymphoma.
+{| class="wikitable sortable"
+|-
+!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
+|-
+|1q||Gain||21-25
+|-
+|6q
+|Loss
+|11-14
+|-
+|7||Gain||
+|-
+|8
+|Gain
+|
+|-
+|12
+|Gain
+|
+|-
+|13q
+|Loss
+|32-34
+|-
+|17p
+|Loss
+|
+|-
+|18
+|Gain
+|
+|}
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+</blockquote>
+==Characteristic Chromosomal or Other Global Mutational Patterns==
+Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
+{| class="wikitable sortable"
+|-
+!Chromosomal Pattern
+!Molecular Pathogenesis
+!Prevalence -
+Common >20%, Recurrent 5-20% or Rare <5% (Disease)
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
+!Clinical Relevance Details/Other Notes
+|-
+|<span class="blue-text">EXAMPLE:</span>
+Co-deletion of 1p and 18q
+|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
+|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
+|<span class="blue-text">EXAMPLE:</span> D, P
+|
+|
+|-
+|<span class="blue-text">EXAMPLE:</span>
+Microsatellite instability - hypermutated
+|
+|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
+|<span class="blue-text">EXAMPLE:</span> P, T
+|
+|
+|-
+|
+|
+|
+|
+|
+|
+|}
+==Gene Mutations (SNV/INDEL)==
+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
+{| class="wikitable sortable"
+|-
+!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
+Common >20%, Recurrent 5-20% or Rare <5% (Disease)
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
+!Clinical Relevance Details/Other Notes
+|-
+|<span class="blue-text">EXAMPLE:</span>''EGFR''
+<br />
+|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
+|<span class="blue-text">EXAMPLE:</span> Oncogene
+|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
+|<span class="blue-text">EXAMPLE:</span> T
+|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
+|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
+|-
+|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
+<br />
+|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
+|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
+|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
+|<span class="blue-text">EXAMPLE:</span> P
+|
+|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
+|-
+|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
+|<span class="blue-text">EXAMPLE:</span> Activating mutations
+|<span class="blue-text">EXAMPLE:</span> Oncogene
+|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
+|<span class="blue-text">EXAMPLE:</span> T
+|
+|
+|-
+|
+|
+|
+|
+|
+|
+|
+|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
+<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>
+{| class="wikitable sortable"
+|-
+!Gene!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
+|-
+|''MYC''||Oncogene||GOF||67%
+|-
+|''ID3<ref>{{Cite journal|last=Richter|first=Julia|last2=Schlesner|first2=Matthias|last3=Hoffmann|first3=Steve|last4=Kreuz|first4=Markus|last5=Leich|first5=Ellen|last6=Burkhardt|first6=Birgit|last7=Rosolowski|first7=Maciej|last8=Ammerpohl|first8=Ole|last9=Wagener|first9=Rabea|date=2012-12|title=Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing|url=https://pubmed.ncbi.nlm.nih.gov/23143595|journal=Nature Genetics|volume=44|issue=12|pages=1316–1320|doi=10.1038/ng.2469|issn=1546-1718|pmid=23143595}}</ref>''
+|Tumour suppressor
+|LOF
+|34%
+|-
+|''DDX3X<ref>{{Cite journal|last=Mo|first=Jie|last2=Liang|first2=Huifang|last3=Su|first3=Chen|last4=Li|first4=Pengcheng|last5=Chen|first5=Jin|last6=Zhang|first6=Bixiang|date=2021-02-24|title=DDX3X: structure, physiologic functions and cancer|url=http://dx.doi.org/10.1186/s12943-021-01325-7|journal=Molecular Cancer|volume=20|issue=1|doi=10.1186/s12943-021-01325-7|issn=1476-4598}}</ref>''
+|Tumour suppressor
+|LOF
+|34%
+|-
+|''BCL6<ref>{{Cite journal|last=Kl|first=Bunting|last2=Am|first2=Melnick|date=2013 Jun|title=New effector functions and regulatory mechanisms of BCL6 in normal and malignant lymphocytes|url=https://pubmed.ncbi.nlm.nih.gov/23725655/|language=en|doi=10.1016/j.coi.2013.05.003|pmc=PMC4075446|pmid=23725655}}</ref>''
+|Oncogene
+|GOF
+|25%
+|-
+|''BCL7A<ref>{{Cite journal|last=Zani|first=V. J.|last2=Asou|first2=N.|last3=Jadayel|first3=D.|last4=Heward|first4=J. M.|last5=Shipley|first5=J.|last6=Nacheva|first6=E.|last7=Takasuki|first7=K.|last8=Catovsky|first8=D.|last9=Dyer|first9=M. J.|date=1996-04-15|title=Molecular cloning of complex chromosomal translocation t(8;14;12)(q24.1;q32.3;q24.1) in a Burkitt lymphoma cell line defines a new gene (BCL7A) with homology to caldesmon|url=https://pubmed.ncbi.nlm.nih.gov/8605326|journal=Blood|volume=87|issue=8|pages=3124–3134|issn=0006-4971|pmid=8605326}}</ref>''
+|Oncogene
+|GOF
+|24%
+|-
+|''FBXO11<ref>{{Cite journal|last=Pighi|first=Chiara|last2=Compagno|first2=Mara|last3=Wang|first3=Qi|last4=Cheong|first4=Taek-Chin|last5=Poggio|first5=Teresa|last6=Langellotto|first6=Fernanda|last7=Francia di Celle|first7=Paola|last8=Zamò|first8=Alberto|last9=Chiarle|first9=Roberto|date=2015-12-03|title=FBXO11, a Regulator of BCL6 Stability, Is Recurrently Mutated in Burkitt Lymphoma|url=http://dx.doi.org/10.1182/blood.v126.23.3673.3673|journal=Blood|volume=126|issue=23|pages=3673–3673|doi=10.1182/blood.v126.23.3673.3673|issn=0006-4971}}</ref>''
+|Tumour suppressor
+|LOF
+|23%
+|-
+|''FOXO1<ref>{{Cite journal|last=Zhou|first=Peixun|last2=Blain|first2=Alex E.|last3=Newman|first3=Alexander M.|last4=Zaka|first4=Masood|last5=Chagaluka|first5=George|last6=Adlar|first6=Filbert R.|last7=Offor|first7=Ugonna T.|last8=Broadbent|first8=Casey|last9=Chaytor|first9=Lewis|date=2019-07-23|title=Sporadic and endemic Burkitt lymphoma have frequent FOXO1 mutations but distinct hotspots in the AKT recognition motif|url=https://pubmed.ncbi.nlm.nih.gov/31300419|journal=Blood Advances|volume=3|issue=14|pages=2118–2127|doi=10.1182/bloodadvances.2018029546|issn=2473-9537|pmc=6650741|pmid=31300419}}</ref>''
+|Oncogene
+|GOF
+|23%
+|-
+|''SMARCA4<ref>{{Cite journal|last=Love|first=Cassandra|last2=Sun|first2=Zhen|last3=Jima|first3=Dereje|last4=Li|first4=Guojie|last5=Zhang|first5=Jenny|last6=Miles|first6=Rodney|last7=Richards|first7=Kristy L.|last8=Dunphy|first8=Cherie H.|last9=Choi|first9=William W. L.|date=2012-12|title=The genetic landscape of mutations in Burkitt lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/23143597|journal=Nature Genetics|volume=44|issue=12|pages=1321–1325|doi=10.1038/ng.2468|issn=1546-1718|pmc=3674561|pmid=23143597}}</ref>''
+|Tumour suppressor
+|LOF
+|23%
+|-
+|''ARID1A<ref>{{Cite journal|last=Love|first=Cassandra|last2=Sun|first2=Zhen|last3=Jima|first3=Dereje|last4=Li|first4=Guojie|last5=Zhang|first5=Jenny|last6=Miles|first6=Rodney|last7=Richards|first7=Kristy L.|last8=Dunphy|first8=Cherie H.|last9=Choi|first9=William W. L.|date=2012-12|title=The genetic landscape of mutations in Burkitt lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/23143597|journal=Nature Genetics|volume=44|issue=12|pages=1321–1325|doi=10.1038/ng.2468|issn=1546-1718|pmc=3674561|pmid=23143597}}</ref>''
+|Tumour suppressor
+|LOF
+|18%
+|-
+|''TP53<ref>{{Cite journal|last=Shannon-Lowe|first=Claire|last2=Rickinson|first2=Alan B.|last3=Bell|first3=Andrew I.|date=2017-10-19|title=Epstein-Barr virus-associated lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/28893938|journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences|volume=372|issue=1732|doi=10.1098/rstb.2016.0271|issn=1471-2970|pmc=5597738|pmid=28893938}}</ref>''
+|Tumour suppressor
+|LOF
+|17%
+|-
+|''CTCF<ref>{{Cite journal|last=Chau|first=Charles M.|last2=Zhang|first2=Xiao-Yong|last3=McMahon|first3=Steven B.|last4=Lieberman|first4=Paul M.|date=2006-06-15|title=Regulation of Epstein-Barr Virus Latency Type by the Chromatin Boundary Factor CTCF|url=https://jvi.asm.org/content/80/12/5723|journal=Journal of Virology|language=en|volume=80|issue=12|pages=5723–5732|doi=10.1128/JVI.00025-06|issn=0022-538X|pmc=PMC1472585|pmid=16731911}}</ref>''
+|Tumour suppressor
+|LOF
+|16%
+|-
+|''CREBBP<ref>{{Cite journal|last=Love|first=Cassandra|last2=Sun|first2=Zhen|last3=Jima|first3=Dereje|last4=Li|first4=Guojie|last5=Zhang|first5=Jenny|last6=Miles|first6=Rodney|last7=Richards|first7=Kristy L.|last8=Dunphy|first8=Cherie H.|last9=Choi|first9=William W. L.|date=2012-12|title=The genetic landscape of mutations in Burkitt lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/23143597|journal=Nature Genetics|volume=44|issue=12|pages=1321–1325|doi=10.1038/ng.2468|issn=1546-1718|pmc=3674561|pmid=23143597}}</ref>''
+|Tumour suppressor
+|LOF
+|15%
+|-
+|''TCL1A<ref>{{Cite journal|last=Aggarwal|first=Mohit|last2=Villuendas|first2=Raquel|last3=Gomez|first3=Gonzalo|last4=Rodriguez-Pinilla|first4=Socorro M|last5=Sanchez-Beato|first5=Margarita|last6=Alvarez|first6=David|last7=Martinez|first7=Nerea|last8=Rodriguez|first8=Antonia|last9=Castillo|first9=Maria E|date=2008-09-26|title=TCL1A expression delineates biological and clinical variability in B-cell lymphoma|url=http://dx.doi.org/10.1038/modpathol.2008.148|journal=Modern Pathology|volume=22|issue=2|pages=206–215|doi=10.1038/modpathol.2008.148|issn=0893-3952}}</ref>''
+|Oncogene
+|GOF
+|15%
+|-
+|''BCR<ref>{{Cite journal|last=Küppers|first=Ralf|date=2005-04|title=Mechanisms of B-cell lymphoma pathogenesis|url=http://dx.doi.org/10.1038/nrc1589|journal=Nature Reviews Cancer|volume=5|issue=4|pages=251–262|doi=10.1038/nrc1589|issn=1474-175X}}</ref>''
+|Oncogene
+|GOF
+|15%
+|-
+|''TCF3<ref>{{Cite journal|last=Schmitz|first=Roland|last2=Young|first2=Ryan M.|last3=Ceribelli|first3=Michele|last4=Jhavar|first4=Sameer|last5=Xiao|first5=Wenming|last6=Zhang|first6=Meili|last7=Wright|first7=George|last8=Shaffer|first8=Arthur L.|last9=Hodson|first9=Daniel J.|date=2012-10-04|title=Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics|url=https://pubmed.ncbi.nlm.nih.gov/22885699|journal=Nature|volume=490|issue=7418|pages=116–120|doi=10.1038/nature11378|issn=1476-4687|pmc=3609867|pmid=22885699}}</ref>''
+|Oncogene
+|GOF
+|14%
+|-
+|''CCND3<ref>{{Cite journal|last=Schmitz|first=Roland|last2=Young|first2=Ryan M.|last3=Ceribelli|first3=Michele|last4=Jhavar|first4=Sameer|last5=Xiao|first5=Wenming|last6=Zhang|first6=Meili|last7=Wright|first7=George|last8=Shaffer|first8=Arthur L.|last9=Hodson|first9=Daniel J.|date=2012-10-04|title=Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics|url=https://pubmed.ncbi.nlm.nih.gov/22885699|journal=Nature|volume=490|issue=7418|pages=116–120|doi=10.1038/nature11378|issn=1476-4687|pmc=3609867|pmid=22885699}}</ref>''
+|Oncogene
+|GOF
+|14%
+|}
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+</blockquote>
+==Epigenomic Alterations==
+Put your text here
+==Genes and Main Pathways Involved==
+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
+{| class="wikitable sortable"
+|-
+!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
+|-
+|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
+|<span class="blue-text">EXAMPLE:</span> MAPK signaling
+|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
+|-
+|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
+|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
+|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
+|-
+|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
+|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
+|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
+|-
+|
+|
+|
+|}
+<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>
+''MYC'' is the most commonly mutated gene in Burkitt lymphoma, such variants lead to constitutive expression of ''MYC'', which drives cell survival. Aberrant somatic hypermutation is understood to be the major cause of ''MYC'' breakpoint formation and the presence of hypermutation in tandem with MYC rearrangement may be detectable if using sequencing methodologies.
+Localised ''TP53'' inactivating mutations or chromosomal deletions involving ''TP53'' are also common in Burkitt lymphoma, and cause abrogation of ''TP53''-dependent apoptotic pathways. Loss of ''TP53'' function through the aforementioned means, or dysregulation due to the mutation of ''TP53'' regulatory elements, is believed to be key to the development of Burkitt lymphoma<ref>{{Cite journal|last=Shannon-Lowe|first=Claire|last2=Rickinson|first2=Alan B.|last3=Bell|first3=Andrew I.|date=2017-10-19|title=Epstein-Barr virus-associated lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/28893938|journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences|volume=372|issue=1732|doi=10.1098/rstb.2016.0271|issn=1471-2970|pmc=5597738|pmid=28893938}}</ref>.
+''TCF3'' or ''ID3'' mutations are seen in approximately 70% of sporadic Burkitt lymphoma. The normal function of transcription factor E2A (encoded by ''TCF3'') is regulation of the differentiation of B-cells in the germinal centre. Mutations in ''TCF3'' leads to reduced affinity for its negative regulator, ''ID3'', promoting constitutive activity. ''TCF3'' promotes B-cell receptor signaling in Burkitt lymphoma, which enhances survival via the PI3 kinase pathway. ''TCF3'' also transactivates ''CCND3'' which encodes cyclin D3 expression, promoting cell cycle progression and proliferation<ref>{{Cite journal|last=Schmitz|first=Roland|last2=Young|first2=Ryan M.|last3=Ceribelli|first3=Michele|last4=Jhavar|first4=Sameer|last5=Xiao|first5=Wenming|last6=Zhang|first6=Meili|last7=Wright|first7=George|last8=Shaffer|first8=Arthur L.|last9=Hodson|first9=Daniel J.|date=2012-10-04|title=Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics|url=https://pubmed.ncbi.nlm.nih.gov/22885699|journal=Nature|volume=490|issue=7418|pages=116–120|doi=10.1038/nature11378|issn=1476-4687|pmc=3609867|pmid=22885699}}</ref>.
+Mutations overall, and in particular in ''TCF3'' and ''ID3'', are less common in endemic  Burkitt lymphoma when compared to sporadic cases. It is postulated that this additional mutational burden may take the place of EBV in sporadic Burkitt lymphomagenesis, given that either mechanism can lead to the activation of B-cell receptor signaling.
+The gene expression and micro-RNA expression profiles of Burkitt lymphoma are different from other lymphomas. The expression profiles of endemic and sporadic BL are also slightly different to each other. There may be grey zones where Burkitt lymphoma is difficult to distinguish from diffuse large B-cell lymphoma based on gene expression, hence expression should not be used as an independent diagnostic tool<ref>{{Cite journal|last=Shannon-Lowe|first=Claire|last2=Rickinson|first2=Alan B.|last3=Bell|first3=Andrew I.|date=2017-10-19|title=Epstein-Barr virus-associated lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/28893938|journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences|volume=372|issue=1732|doi=10.1098/rstb.2016.0271|issn=1471-2970|pmc=5597738|pmid=28893938}}</ref>.
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+</blockquote>
+==Genetic Diagnostic Testing Methods==
+Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
+==Familial Forms==
+The X-linked lymphoproliferative syndrome 'Duncan disease', is associated with SH2D1A mutations. Individuals with this condition are at greatly increased risk of developing Burkitt lymphoma.
+==Additional Information==
+Put your text here
+==Links==
+[[HAEM5:High grade B-cell lymphoma with 11q aberrations]]
+==References==
+(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />
+<br />
+==Notes==
+<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
+Prior Author(s):
+<nowiki>*</nowiki>''Citation of this Page'': “Burkitt lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Burkitt_lymphoma</nowiki>.
+==Other Sections==
+Cancer Sub-Classification/Subtype
+Burkitt lymphoma
+Definition/Description of Disease
+Burkitt lymphoma is a clinically aggressive but curable lymphoma with three aetiologically distinct subtypes, these being endemic, sporadic and immunodeficiency-associated Burkitt lymphoma. Infection with Epstein-Bar virus (EBV), also known as human herpesvirus 4, is seen all three subtypes, but is most strongly associated with endemic Burkitt Lymphoma. Detectable EBV infection is not essential for diagnosis, and may not be the cause in all cases; the frequency of EBV infection varies according to the epidemiological subtype of Burkitt lymphoma. The clinical presentation often involves extra-nodal sites but the disease can also present as an acute leukaemia.
+Synonyms/Terminology
+Burkitt cell leukaemia
+Obsolete terms
+*Burkitt tumour
+*Malignant lymphoma, undifferentiated, Burkitt type
+*Malignant lymphoma, small non-cleaved, Burkitt type
+Epidemiology/Prevalence
+Endemic Burkitt lymphoma
+*Highly associated with Epstein-Barr virus (EBV genome present in >95% of neoplastic cells) and ''Plasmodium falciparum'' infection
+*Occurs in equatorial Africa and Papua New Guinea, with a distribution that overlaps with regions endemic for malaria
+*Demographics: peak incidence among children aged 4-7 years
+*The incidence is higher in males than females, at a ratio of 2:1
+Sporadic Burkitt lymphoma
+*EBV detected in 20-30% of cases, proportion of EBV positive cases appears to be much higher in adults than in children
+*Occurs worldwide
+*Western Europe and USA: low incidence, accounting for only 1-2% of all lymphomas overall (30-50% of all childhood lymphomas)
+*South America and northern Africa: incidence between that of sporadic Burkitt lymphoma in developed countries and endemic Burkitt lymphoma
+*Demographics: peak incidence among children and young adults (median age 30 years, with separate incidence peak in elderly patients)
+*M:F 2-3:1
+Immunodeficiency-associated Burkitt lymphoma
+*EBV detected in 25-40% of cases
+*Associated with HIV infection (most commonly) and other forms of immunosuppression
+*Occurs early in the course of HIV infection, when CD4+ T cell counts are still high
+*Increased risk of developing Burkitt lymphoma has persisted across the pre-and post-HAART eras
+[[Category:HAEM5]]
+[[Category:DISEASE]]
+[[Category:Diseases B]]