Deletion of Ribosomal Protein Genes is a Common Vulnerability in Human Cancer, Especially in Concert with Mutations

Overview

Journal EMBO Mol Med

Specialty Molecular Biology

Date 2017 Mar 8

PMID 28264936

Citations 62

Authors

Ram Ajore

David Raiser

Marie McConkey

Magnus Joud

Bernd Boidol

Brenton Mar

Gordon Saksena

David M Weinstock

Scott Armstrong

Steven R Ellis

Benjamin L Ebert

Bjorn Nilsson

Affiliations

Soon will be listed here.

Abstract

Heterozygous inactivating mutations in ribosomal protein genes (RPGs) are associated with hematopoietic and developmental abnormalities, activation of p53, and altered risk of cancer in humans and model organisms. Here we performed a large-scale analysis of cancer genome data to examine the frequency and selective pressure of RPG lesions across human cancers. We found that hemizygous RPG deletions are common, occurring in about 43% of 10,744 cancer specimens and cell lines. Consistent with p53-dependent negative selection, such lesions are underrepresented in -intact tumors ( ≪ 10), and shRNA-mediated knockdown of RPGs activated p53 in -wild-type cells. In contrast, we did not see negative selection of RPG deletions in -mutant tumors. RPGs are conserved with respect to homozygous deletions, and shRNA screening data from 174 cell lines demonstrate that further suppression of hemizygously deleted RPGs inhibits cell growth. Our results establish RPG haploinsufficiency as a strikingly common vulnerability of human cancers that associates with mutations and could be targetable therapeutically.

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