An APOBEC Cytidine Deaminase Mutagenesis Pattern is Widespread in Human Cancers

Overview

Journal Nat Genet

Specialty Genetics

Date 2013 Jul 16

PMID 23852170

Citations 710

Authors

Steven A Roberts

Michael S Lawrence

Leszek J Klimczak

Sara A Grimm

David Fargo

Petar Stojanov

Adam Kiezun

Gregory V Kryukov

Scott L Carter

Gordon Saksena

Shawn Harris

Ruchir R Shah

Michael A Resnick

Gad Getz

Dmitry A Gordenin

Affiliations

Soon will be listed here.

Abstract

Recent studies indicate that a subclass of APOBEC cytidine deaminases, which convert cytosine to uracil during RNA editing and retrovirus or retrotransposon restriction, may induce mutation clusters in human tumors. We show here that throughout cancer genomes APOBEC-mediated mutagenesis is pervasive and correlates with APOBEC mRNA levels. Mutation clusters in whole-genome and exome data sets conformed to the stringent criteria indicative of an APOBEC mutation pattern. Applying these criteria to 954,247 mutations in 2,680 exomes from 14 cancer types, mostly from The Cancer Genome Atlas (TCGA), showed a significant presence of the APOBEC mutation pattern in bladder, cervical, breast, head and neck, and lung cancers, reaching 68% of all mutations in some samples. Within breast cancer, the HER2-enriched subtype was clearly enriched for tumors with the APOBEC mutation pattern, suggesting that this type of mutagenesis is functionally linked with cancer development. The APOBEC mutation pattern also extended to cancer-associated genes, implying that ubiquitous APOBEC-mediated mutagenesis is carcinogenic.

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