Crick Lecture 2014: How Aneuploidy Drives Cancer

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• Stephen Elledge, Gregor Mendel Professor of Genetics, Department of Genetics, Harvard Medical School
• Friday 19 September 2014, 16:15-18:00
• Max Perutz Lecture Theatre, Medical Research Council (MRC) (MRC Laboratory of Molecular Biol.

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Aneuploidy has been recognized as a hallmark of cancer for over 100 years, yet no general theory to explain the recurring patterns of aneuploidy in cancer has emerged. We developed Tumor Suppressor and Oncogene (TUSON) Explorer, a computational method that analyzes the patterns of mutational signatures in tumors and predicts the likelihood that any individual gene functions as a tumor suppressor (TSG) or oncogene (OG). By analyzing >8200 tumor-normal pairs we provide statistical evidence suggesting many more genes possess cancer driver properties than anticipated, forming a continuum of oncogenic potential. Integrating our driver predictions with information on somatic copy number alterations, we find that the distribution and the potency of TSGs (STOP genes), OGs and essential genes (GO genes) on chromosomes can predict the complex patterns of aneuploidy and copy number variation characteristic of cancer genomes. We propose that the cancer genome is shaped through a process of cumulative haploinsufficiency and triplosensitivity. We are now assessing how aneuploidy drives cancer and the potency with which it does so. Ramifications of aneuploidy will be discussed.

This talk is part of the MRC LMB Seminar Series series.

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