Oncotarget

Research Papers:

Recurrent targets of aberrant somatic hypermutation in lymphoma

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 JM Jones _

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Oncotarget. 2012; 3:1308-1319. https://doi.org/10.18632/oncotarget.653

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Abstract

Alireza Hadj Khodabakhshi1,Ryan D. Morin1, Anthony P. Fejes1, Andrew J. Mungall1, Karen L. Mungall1, Madison Bolger-Munro1, Nathalie A. Johnson2, Joseph M. Connors2, Randy D. Gascoyne2,3, Marco A. Marra1,4, Inanc Birol1, Steven J. M. Jones1,4,5

1 Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada

2 Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada

3 Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada

4 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada

5 Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada

Correspondence:

Steven J. M. Jones, email:

Keywords: Aberrant somatic hypermutation, Genome wide study, Diffuse large B-cell lymphoma, Genomic rearrangements

Received: September 13, 2012, Accepted: Ocotber 10, 2012, Published: October 12, 2012

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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