Balca R. Mardin

Abstract Cancer mutations perturb key processes, driving uncontrolled cell proliferation. With critical roles of enzymes in cell function and growth, we hypothesized that cancer driver mutations alter specific and recurrent enzymatic functions. Leveraging large pan-cancer genomic datasets and curated mutation catalogs, we identified frequent mutations in helicases, enzymes involved in nucleic acid unwinding and processing.

Abstract An important goal in cancer research is to identify driver genes and mutations. Reasoning that such mutations often alter enzymatic functions, we investigated the cancer driver role of enzyme families. Using pan-cancer genomic data and established driver mutation catalogues, we found an unexpectedly high rate of mutations in helicases, making helicases the most frequently mutated enzyme family in cancer.

The consequence of chromosome instability on tumor development continues to stand at the center of a scientific debate. Depending on genetic- and tissue-specific contexts, CIN-associated gene de-regulations promote, suppress, or have no effect on spontaneous tumorigenesis (Janssen and Medema, 2013xGenetic instability: tipping the balance. Janssen, A. and Medema, R.H. Oncogene.