| dc.description.abstract | e most common pedi atric cancer in malaria-endemic equatorial Africa and nearly
always contains Epstein–Barr virus (EBV), unlike sporadic Burkitt
lymphoma (sBL) that occurs with a lower incidence in developed
countries. Given these differences and the variable clinical pre sentation and outcomes, we sought to further understand path ogenesis by investigating transcriptomes using RNA sequencing
(RNAseq) from multiple primary eBL tumors compared with sBL
tumors. Within eBL tumors, minimal expression differences were
found based on: anatomical presentation site, in-hospital survival
rates, and EBV genome type, suggesting that eBL tumors are
homogeneous without marked subtypes. The outstanding differ ence detected using surrogate variable analysis was the signifi cantly decreased expression of key genes in the immunoprotea some complex (PSMB9/b1i, PSMB10/b2i, PSMB8/b5i, and
PSME2/PA28b) in eBL tumors carrying type 2 EBV compared
with type 1 EBV. Second, in comparison with previously pub lished pediatric sBL specimens, the majority of the expression and
pathway differences was related to the PTEN/PI3K/mTOR sig naling pathway and was correlated most strongly with EBV
status rather than geographic designation. Third, common
mutations were observed significantly less frequently in eBL
tumors harboring EBV type 1, with mutation frequencies sim ilar between tumors with EBV type 2 and without EBV. In
addition to the previously reported genes, a set of new genes
mutated in BL, including TFAP4, MSH6, PRRC2C, BCL7A,
FOXO1, PLCG2, PRKDC, RAD50, and RPRD2, were identified.
Overall, these data establish that EBV, particularly EBV type 1,
supports BL oncogenesis, alleviating the need for certain driver
mutations in the human genome.
Implications: Genomic and mutational analyses of Burkitt lym phoma tumors identify key differences based on viral content and
clinical outcomes suggesting new avenues for the development of
prognostic molecular biomarkers and therapeutic interventions.
Mol Cancer Res; 15(5); 563–76. 2017 AACR. | en_US |
