Recurrent Targets of Aberrant Somatic Hypermutation in Lymphoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2012 Nov 8

PMID 23131835

Citations 69

Authors

Alireza Hadj Khodabakhshi

Ryan D Morin

Anthony P Fejes

Andrew J Mungall

Karen L Mungall

Madison Bolger-Munro

Nathalie A Johnson

Joseph M Connors

Randy D Gascoyne

Marco A Marra

Inanc Birol

Steven J M Jones

Affiliations

Soon will be listed here.

Abstract

Somatic hypermutation (SHM) in the variable region of immunoglobulin genes (IGV) naturally occurs in a narrow window of B cell development to provide high-affinity antibodies. However, SHM can also aberrantly target proto-oncogenes and cause genome instability. The role of aberrant SHM (aSHM) has been widely studied in various non-Hodgkin's lymphoma particularly in diffuse large B-cell lymphoma (DLBCL). Although, it has been speculated that aSHM targets a wide range of genome loci so far only twelve genes have been identified as targets of aSHM through the targeted sequencing of selected genes. A genome-wide study aiming at identifying a comprehensive set of aSHM targets recurrently occurring in DLBCL has not been previously undertaken. Here, we present a comprehensive assessment of the somatic hypermutated genes in DLBCL identified through an analysis of genomic and transcriptome data derived from 40 DLBCL patients. Our analysis verifies that there are indeed many genes that are recurrently affected by aSHM. In particular, we have identified 32 novel targets that show same or higher level of aSHM activity than genes previously reported. Amongst these novel targets, 22 genes showed a significant correlation between mRNA abundance and aSHM.

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