Unknown,Transcriptomics,Genomics,Proteomics

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Genetic Heterogeneity of DLBCL


ABSTRACT: 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. 21 DLBCL cell lines and 70 DLBCL patient samples.

ORGANISM(S): Homo sapiens

SUBMITTER: Dereje Jima 

PROVIDER: E-GEOD-43606 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genetic heterogeneity of diffuse large B-cell lymphoma.

Zhang Jenny J   Grubor Vladimir V   Love Cassandra L CL   Banerjee Anjishnu A   Richards Kristy L KL   Mieczkowski Piotr A PA   Dunphy Cherie C   Choi William W   Au Wing Yan WY   Srivastava Gopesh G   Lugar Patricia L PL   Rizzieri David A DA   Lagoo Anand S AS   Bernal-Mizrachi Leon L   Mann Karen P KP   Flowers Christopher C   Naresh Kikkeri K   Evens Andrew A   Gordon Leo I LI   Czader Magdalena M   Gill Javed I JI   Hsi Eric D ED   Liu Qingquan Q   Fan Alice A   Walsh Katherine K   Jima Dereje D   Smith Lisa L LL   Johnson Amy J AJ   Byrd John C JC   Luftig Micah A MA   Ni Ting T   Zhu Jun J   Chadburn Amy A   Levy Shawn S   Dunson David D   Dave Sandeep S SS  

Proceedings of the National Academy of Sciences of the United States of America 20130104 4


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 tha  ...[more]

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