The Somatic Mutation Profiles of 2,433 Breast Cancers Refines Their Genomic and Transcriptomic Landscapes

Overview

Journal Nat Commun

Specialty Biology

Date 2016 May 11

PMID 27161491

Citations 923

Authors

Bernard Pereira

Suet-Feung Chin

Oscar M Rueda

Hans-Kristian Moen Vollan

Elena Provenzano

Helen A Bardwell

Michelle Pugh

Linda Jones

Roslin Russell

Stephen-John Sammut

Dana W Y Tsui

Bin Liu

Sarah-Jane Dawson

Jean Abraham

Helen Northen

John F Peden

Abhik Mukherjee

Gulisa Turashvili

Andrew R Green

Steve McKinney

Arusha Oloumi

Sohrab Shah

Nitzan Rosenfeld

Leigh Murphy

David R Bentley

Ian O Ellis

Arnie Purushotham

Sarah E Pinder

Anne-Lise Borresen-Dale

Helena M Earl

Paul D Pharoah

Mark T Ross

Samuel Aparicio

Carlos Caldas

Affiliations

Soon will be listed here.

Abstract

The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intra-tumour heterogeneity using mutant-allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13-14 or 8q24). High levels of intra-tumour heterogeneity are in general associated with a worse outcome, but highly aggressive tumours with 11q13-14 amplification have low levels of intra-tumour heterogeneity. These results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies.

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