The Somatic Cancer Genome

New genome sequencing technologies have led to an explosion of cancer genome sequence information, resulting in new insights into the genetic basis of cancer. This talk will review recent advances in somatic cancer genome analysis, with particular emphasis on hematological malignancies including diffuse large B-cell lymphoma and multiple myeloma. New analytical approaches have led to both a refined ability to distinguish true drivers of cancer from mere passenger mutations and to a better understanding of what scale of cancer genome sequencing will be required to “complete” a cancer genome atlas of mutations. While many of the recurrently mutated genes in cancer have known function, many remain uncharacterized. As such, a new kind of follow-up research activity is required – one that can bring systematic, high throughput biology methods to bear on elucidating mutant allele function and their potential as therapeutic targets. Efforts to pilot such a “Target Accelerator” will be presented, with particular emphasis on use of the Connectivity Map/Library of integrated cellular signatures (LINCS) resource to systematically connect mutant alleles to pathways and to potential therapeutic strategies.