Association of somatic mutations of ADAMTS genes with chemotherapy sensitivity and survival in high-grade serous ovarian carcinoma

Abstract

IMPORTANCE: Chemotherapy response in the majority of patients with ovarian cancer remains unpredictable. OBJECTIVE:To identify novel molecular markers for predicting chemotherapy response in patients with ovarian cancer. DESIGN, SETTING, AND PARTICIPANTS: Observational study of genomics and clinical data of high-grade serous ovarian cancer cases with genomic and clinical data made public between 2009 and 2014 via the Cancer Genome Atlas project. MAINOUTCOMES ANDMEASURES: Chemotherapy response (primary outcome) and overall survival (OS), progression-free survival (PFS), and platinum-free duration (secondary outcome). RESULTS: In 512 patients with ovarian cancer with available whole-exome sequencing data, mutations from 8 members ofthe ADAMTS family (ADAMTS mutations) with an overall mutation rate of approximately 10.4% were associated with a significantly higher chemotherapy sensitivity (100% for ADAMTS-mutatedvs 64% for ADAMTS wild-type cases; P