Minnelide: A promising new therapy for ovarian cancer

integrative genomic analyses of publicly available mutational and DNA copy number data to identify hypermutated cancers and to infer underlying mutational processes driving hypermutation. Results: We identified 395 hypermutated tumors in 16 diverse tumor types representing ~3.6% of all cancers. Of these, 47% of patient tumors possessed somatic hypermutation that could not be explained by an established exogenous mutagen, environmental exposure, or known defect in DNA repair. Hypermutationwasmost common in endometrial cancer andwas observed in 69% of samples. Defects in DNA polymerase episilon and/or in mismatch repair drives hypermutation in endometrial cancers. Colorectal and stomach carcinomas also had hypermutation as a recurringmutational subtype observed in 26% and 24% of samples, respectively. Despite the identification of hypermutation in disparate tumor types, ovarian and cervical carcinomas did not have any samples with this phenotype (p b 0.0001). We used allelic abundance data to help determine the temporal sequence of somatic events in endometrial cancers with multiple defects potentially contributing to the observed hypermutation. Conclusion: Somatic hypermutation is most commonly found in endometrial, colorectal and stomach carcinomas but absent in ovarian and cervix carcinomas. We exploit big data to explore uncommon cancer phenotypes like somatic hypermutation across cancer types, bridging the gap between complex mutational landscapes to help inform clinical decisions.