604 Cancer Genomics, Epigenetics and Genomic Instability. Mutational Processes Shaping the Genomes of Twenty-One Breast Cancers

Publication
European Journal of Cancer, 48 S144. https://doi.org/10.1016/S0959-8049(12)71258-3

Abstract: All cancers carry somatic mutations. The set of somatic mutations observed in a cancer genome is the aggregate outcome of the activity of one or more biological processes that have been operative over the lifetime of a patient. Each of these biological processes can be characterised by the pattern of mutations that it leaves on the cancer genome. The pattern of mutations or mutational signature characterising each process will be determined both by the underlying mechanisms of DNA damage and of DNA repair that constitute the biological process. The final catalogue of somatic mutations observed in a cancer genome will thus be determined by the strength and duration of exposure to each of the biological processes that have been operative in that cancer. We set out to extract the mutational signatures characterising the biological processes that have been operative in the 21 breast cancers studied. We generated catalogues of somatic mutation of all classes of mutation from twenty-one whole-genome sequenced breast cancers using an integrated suite of bioinformatic algorithms. Mathematical methods were applied in order to extract features of the underlying mutational signatures. Multiple distinct substitution signatures and their relative contribution to each cancer genome, were discernible. In addition, other distinctive phenomena have been unearthed by analyses of breast cancer genomes at this scale. This study harnesses the full scale of whole-genome sequencing technology providing insights into hitherto unrecognised mutational signatures present in breast cancer genomes

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