Expression profiling by array Genome variation profiling by SNP array SNP genotyping by SNP array
Summary
We analysed a cohort of 75 BRCA1, BRCA2 and non-BRCA1/2 breast tumors by gene expression profiling and found that 74% BRCA1 tumors were basal-like, 73% of BRCA2 tumors were luminal A or B, and 52% non-BRCA1/2 tumors were luminal A. Thirty-four tumors were also analysed by single nucleotide polymorphism-comparative genomic hybridization (SNP-CGH) arrays. Copy number data could predict whether a tumor was basal-like or luminal with high accuracy, but could not predict its mutation class. Basal-like BRCA1 and basal-like non-BRCA1 tumors 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 tumors (1q and 17q). Regions of homozygous loss associated with decreased expression of potential tumor suppressor genes were also detected, including in basal tumors (5q and 9p), and basal and luminal tumors (10q). This study highlights the heterogeneity of familial tumors and the clinical consequences for treatment and prognosis.
Overall design
RNA was extracted from 75 Familial breast tumours, which were more than 50% tumour cells, comprising BRCA1 (19), BRCA2 (30), non-BRCA1/2 (25) and one familial tumour of unknown mutation status. DNA was also extracted from 34 of these samples which were more than 75% tumour.
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