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Waddell, N.; Arnold, J.; Cocciardi, S.; Silva, L. da; Marsh, A.; Riley, J.; ... ; kConFab Investigators (2010)

Subtypes of familial breast tumours revealed by expression and copy number profiling

Article / Letter to editor
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...Show moreExtensive 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.Show less
BRCA1 and BRCA2 Molecular subtypes Familial breast cancer Gene expression Copy number aberrations comparative genomic hybridization brca1 promoter methylation hidden-markov model snp genotyping data gene-expression sporadic breast molecular portraits tissue microarray ovarian-cancer immunohistochemical markers
All authors
Waddell, N.; Arnold, J.; Cocciardi, S.; Silva, L. da; Marsh, A.; Riley, J.; Johnstone, C.N.; Orloff, M.; Assie, G.; Eng, C.; Reid, L.; Keith, P.; Yan, M.; Fox, S.; Devilee, P.; Godwin, A.K.; Hogervorst, F.B.L.; Couch, F.; Grimmond, S.; Flanagan, J.M.; Khanna, K.; Simpson, P.T.; Lakhani, S.R.; Chenevix-Trench, G.; kConFab Investigators
Date
2010-10-31
Journal
Breast Cancer Research and Treatment
Volume
123
Issue
3
Pages
661 - 677
DOI
doi:10.1007/s10549-009-0653-1