Comment[ArrayExpressAccession] E-MTAB-1088 Investigation Title 17 Breast Cancer Genome Illumina Expression Data Comment[Submitted Name] 17 Breast Cancer Genome Illumina Expression Data Experiment Description Cancer evolves dynamically, as clonal expansions supersede or overlap one another, driven by shifting selective pressures, mutational processes and disrupted cancer genes. These processes mark the genome, such that a cancerÕs life history is encrypted in the timing, ploidy, clonality and patterns of somatic mutation. We developed bioinformatic algorithms to decipher this narrative, and applied them to 21 breast cancer genomes. We find that mutational processes evolve across the lifespan of a breast tumor, with cancer-specific signatures of point mutations and chromosomal instability often emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, providing insight into the dynamics of clonal expansion in breast cancer. Most point mutations are found in just a fraction of tumor cells, together with frequent variegation in chromosomal copy number. Every tumor studied here has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent lineages of cells that are capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis. Experimental Design individual_genetic_characteristics_design reference_design co-expression_design Comment[AEExperimentType] transcription profiling by array Comment[AEExperimentDisplayName] Transcription profiling by array of 17 human breast cancer samples Experimental Factor Name INDIVIDUAL Experimental Factor Type individual Quality Control Type Public Release Date 2013-04-16 Person Last Name McLaren Person First Name Stuart Person Mid Initials R Person Email sm2@sanger.ac.uk Person Phone +44 (0) 1223 494753 Person Address The wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK Person Affiliation The Wellcome Trust Sanger Institute Person Roles submitter Protocol Name P-MTAB-26609 Protocol Description Samples were selected on the basis of a pathological review and DNA/RNA was extracted using a traditional phenol or TRIzol method by which ever institute held the tissue. The subsequent genomic DNA and RNA samples were shipped to the Sanger Institute for array analysis. SDRF File E-MTAB-1088.sdrf.txt