HAEM5:Burkitt lymphoma: Difference between revisions

{{DISPLAYTITLE:Burkitt lymphoma}}

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==Primary Author(s)*==

==Definition / Description of Disease==

==Synonyms / Terminology==

==Clinical Features==

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|'''Signs and Symptoms'''

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|'''Laboratory Findings'''

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Patients often present with bulky disease and high tumour burden, showing rapid clinical progression. The typically involved anatomical sites are different for the three subtypes. At presentation, 30% have localised (stage I or II) disease and 70% have advanced (stage III or IV) disease, according to the revised international paediatric non-Hodgkin lymphoma staging system.  

!Notes

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|Yes

|No

|Yes

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).

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.   

* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

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

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!Notes

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7

chr7:1- 159,335,973 [hg38]

chr7

|Yes

|No

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 reference).

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8

chr8:1-145,138,636 [hg38]

chr8

|No

|No

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

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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.  

==Characteristic Chromosomal Patterns==

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!Notes

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Co-deletion of 1p and 18q

|No

|No

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

==Gene Mutations (SNV / INDEL)==

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EGFR; Exon 20 mutations

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==Genes and Main Pathways Involved==

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

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''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.