Objective: The standard treatment for high grade ovarian serous cancer (HG-OSC) is aggressive cytoreductive surgery followed by platinum based chemotherapy. However, approximately 30% of patients exhibit platinum resistance, and those patients show aggressive clinical courses. Currently, it is difficult to predict which HG-OSC patients will respond to platinum-based chemotherapy.
Methods: We analyzed whole exome sequences for 174 HG-SOC patients using data obtained from The Cancer Genome Atlas (TCGA) data portal regarding platinum response. Patients were categorized as having either hypermutation or hypomutation according to the number of mutations in their sample.
Results: HG-SOC showed multiple somatic mutations in individual patients with an average mutated gene number of 61.9. The mean mutation number per patient significantly differed between the platinum sensitive and resistant groups (P<0.001). Patients who were platinum sensitive were more likely to have somatic hypermutation in their cancer cells and multivariate logistic regression analysis revealed that somatic hypermutation was an independent factor for risk estimation of platinum sensitivity (odds ratio [OR]=3.616; P=0.002). In multivariate Cox hazard analysis, we identified that somatic hypermutation, as well as platinum response and surgical outcome, were independent prognostic factors in HG-OSC (overall survival, P=0.012; progression free survival, P=0.036).
Conclusions: Somatic hypermutation was significantly associated with platinum sensitivity and was an independent prognostic factor in HG-OSC patients treated with platinum based chemotherapy.
Copyright © 2012 Elsevier Inc. All rights reserved.