Comprehensive molecular portraits of human breast tumors
We analyzed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, mRNA 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 contributed by stromal/microenvironmental elements, and integrated analyses identified specific signaling pathways dominant in each molecular subtype including a HER2/p-HER2/HER1/p-HER1 signature within the HER2-Enriched expression subtype. Comparison of Basal-like breast tumors with high-grade Serous Ovarian tumors showed many molecular commonalities, suggesting a related etiology and similar therapeutic opportunities. The biologic 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 biologic subtypes of breast cancer.
Associated Data Files
These data represent a data freeze from November 11, 2011. Please note that more recent data are available via the TCGA Data Portal.
Sample Lists - below are links to cumulative list of samples for the publication
Final Full BRCA Sample Summary
Individual Analysis Sample Summaries
Mutations - Level 2 MAF archives containing exome-based somatic mutations
File used in manuscript
Mutations - Publicly accessible MAF archives
The mutations in this MAF archive are a subset of those in the controlled access archive. The mutations include only those that have been verified as somatic. Mutations that could not be verified as somatic have been removed.
Mutations - Germline MAF File (controlled access)
This file contain germline mutations and is access controlled. If you need to obtain access, see this link for instructions