HAEM5:Burkitt lymphoma: Difference between revisions

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

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|Subtype(s)

|Burkitt lymphoma

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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

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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.  

|}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.

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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.   

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==Notes==

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