Comprehensive molecular portraits of human breast tumours

Koboldt D C; Fulton R S; McLellan M D; Schmidt H; Kalicki Veizer J; McMichael J F; Fulton L L; Dooling D J; Ding L; Mardis E R; Wilson R K; Ally A; Balasundaram M; Butterfield Y S N; Carlsen R; Carter C; Chu A; Chuah E; Chun H J E; Coope R J N; Dhalla N; Guin R; Hirst C; Hirst M; Holt R A; Lee D; Li H I; Mayo M; Moore R A; Mungall A J; Pleasance E; Robertson A G; Schein J E; Shafiei A; Sipahimalani P; Slobodan J R; Stoll D; Tam A; Thiessen N; Varhol R J

Scopus

Harvard Medical School; The University of Chicago; MIT; University of North Carolina at Chapel Hill; Duke University Medical Center; National Institutes of Health; UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER; University of California; Stanford University Medical Center; Memorial Sloan-Kettering Cancer Center; Oregon Health and Science University; Mayo Clinic; University of California，San Francisco; University of California San Francisco; M.D.Anderson Cancer Center; Washington University School of Medicine; MD.Anderson Cancer center; The Ohio State University; Oregon Health & Science University; The University of North Carolina at Chapel Hill; Roswell Park Cancer Institute; MD Anderson Cancer Center; University of Texas MD Anderson Cancer Center; Indiana university School of medicine; Baylor college of medicine; Lineberger Comprehensive Cancer Center; University of Miami, Miller School of Medicine; The University of Texas M.D anderson Cancer Center; Baylor college of Medicine; The University of North carolina at Chapel Hill; University of Texas, M.D. Anderson Cancer Center; Indiana University School of Medicine; The University of Texas M.D Anderson Cancer Center; university of chicago; University of Texas M. D. Anderson Cancer Center; Harvard medical school; harvard university; Memorial Sloan-Kettering　Cancer Center; Department of Medicine, Harvard Medical School; The University of Texas M.D.Anderson Cancer Center; The University of Texas MD Anderson Cancer Center; Ohio state university; University of Texas M.D.Anderson cancer center; The University of Texas, MD Anderson Cancer Center; University of Texas, MD Anderson Cancer Center; 1; University of Texas,M.D.Anderson Cancer Center; M.D. Anderson cancer center; harvard medical school; Stanford University medical center; Duke University medical center; Memorial Sloan-kettering Cancer center; The university of Texas,M.D.Anderson Cancer Center; university of pittsburgh; the university of Texas MD Anderson Cancer Center; Md anderson cancer center; university of california; Washington University ,School of Medicine; University of Pittsburgh Medical Center; University Of Texas MD Anderson Cancer Center; University of Texas M.D.Anderson Cancer Center; University of Miami Miller School of Medicine; University of southern California; new; BAYLOR COLLEGE OF MEDICINE; 5; United States

摘要

We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at.10 incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.

摘要

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