HAEM5:Burkitt lymphoma: Difference between revisions

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.  

Due to the high chemosensitivity of the tumour, treatment of Burkitt Lymphoma with chemotherapy can lead to rapid tumour cell death and an acute tumour lysis syndrome secondary to this.  

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==Sites of Involvement==

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.   

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

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* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

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.

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

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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.  

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==Characteristic Chromosomal Patterns==

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|14%

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==Epigenomic Alterations==

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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.   

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>.  

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==Genetic Diagnostic Testing Methods==