1 research outputs found
Genetic heterogeneity of diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common form
of lymphoma in adults. The disease exhibits a striking heterogeneity
in gene expression profiles and clinical outcomes, but its
genetic causes remain to be fully defined. Through whole genome
and exome sequencing, we characterized the genetic diversity of
DLBCL. In all, we sequenced 73 DLBCL primary tumors (34 with
matched normal DNA). Separately, we sequenced the exomes of
21 DLBCL cell lines. We identified 322 DLBCL cancer genes that
were recurrently mutated in primary DLBCLs. We identified recurrent
mutations implicating a number of known and not previously
identified genes and pathways in DLBCL including those related to
chromatin modification (ARID1A and MEF2B), NF-κB (CARD11 and
TNFAIP3), PI3 kinase (PIK3CD, PIK3R1, and MTOR), B-cell lineage
(IRF8, POU2F2, and GNA13), and WNT signaling (WIF1). We also
experimentally validated a mutation in PIK3CD, a gene not previously
implicated in lymphomas. The patterns of mutation demonstrated
a classic long tail distribution with substantial variation
of mutated genes from patient to patient and also between published
studies. Thus, our study reveals the tremendous genetic
heterogeneity that underlies lymphomas and highlights the need
for personalized medicine approaches to treating these patients