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Waddell N, Arnold J, Cocciardi S, da Silva L, Marsh A, Riley J, Johnstone CN, Orloff M, Assie G, Eng C, Reid L, Keith P, Yan M, Fox S, Devilee P, Godwin AK, Hogervorst FB, Couch F, kConFab Investigators, Grimmond S, Flanagan JM, Khanna K, Simpson PT, Lakhani SR, Chenevix-Trench G
Subtypes of familial breast tumours revealed by expression and copy number profiling
Breast Cancer Research and Treatment (2010) 123:661-677.
Extensive expression profiling studies have shown that sporadic breast cancer is composed of five clinically relevant molecular subtypes. However, although BRCA1-related tumours are known to be predominantly basal-like, there are few published data on other classes of familial breast tumours. We analysed a cohort of 75 BRCA1, BRCA2 and non-BRCA1/2 breast tumours by gene expression profiling and found that 74% BRCA1 tumours were basal-like, 73% of BRCA2 tumours were luminal A or B, and 52% non-BRCA1/2 tumours were luminal A. Thirty-four tumours were also analysed by single nucleotide polymorphism-comparative genomic hybridization (SNP-CGH) arrays. Copy number data could predict whether a tumour was basal-like or luminal with high accuracy, but could not predict its mutation class. Basal-like BRCA1 and basal-like non-BRCA1 tumours were very similar, and contained the highest number of chromosome aberrations. We identified regions of frequent gain containing potential driver genes in the basal (8q and 12p) and luminal A tumours (1q and 17q). Regions of homozygous loss associated with decreased expression of potential tumour suppressor genes were also detected, including in basal tumours (5q and 9p), and basal and luminal tumours (10q). This study highlights the heterogeneity of familial tumours and the clinical consequences for treatment and prognosis.
Publication Date: 2010-10-01.
PMCID: Not required
Last updated on Wednesday, February 05, 2020