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ADAMTS mutations may predict chemotherapy response in ovarian cancer
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The presence of ADAMTS somatic mutations may improve chemotherapy sensitivity and prolong OS in patients with ovarian cancer who do not possess BRCA1 or BRCA2 mutations, according to the results of an observational study.
Chemotherapy response remains unpredictable among patients with ovarian cancer. Patients with germline or somatic BRCA1 or BRCA2 mutations tend to have better treatment response and increased survival outcomes; however, these mutations only occur in approximately 20% of the patient population, according to study background.
Wei Zhang, PhD, of the department of pathology at The University of Texas MD Anderson Cancer Center, and colleagues conducted an observational study to determine whether other novel molecular markers exist to predict chemotherapy response in patients with ovarian cancer. The researchers used genomic and clinical data from The Cancer Genome Atlas project on patients with high-grade serous ovarian cancer.
Chemotherapy response served as the primary endpoint. OS, PFS and platinum-free treatment duration served as secondary endpoints.
Researchers evaluated whole-exome sequencing data from 512 patients with ovarian cancer. Overall, mutations from eight members of the ADAMTS family — with an overall mutation rate of 10.4% (n = 53 cases) — corresponded with a significantly increased chemotherapy sensitivity compared with ADAMTS wild-type cases (100% vs. 64%; P < .001).
The presence of ADAMTS mutations also conferred a longer median platinum-free treatment duration compared with wild-type cases (21.7 months vs. 10.1 months; P = .001).
Patients who harbored ADAMTS mutations achieved a median OS of 58 months, compared with a 41.3-month median OS in ADAMTS wild-type patients (HR = 0.54; 95% CI, 0.42-0.89). Further, patients with ADAMTS mutations also achieved significantly prolonged median PFS (31.8 months vs. 15.3 months; HR = 0.42; 95% CI, 0.38-0.7).
After adjusting for additional factors — including BRCA1 and BRCA2 mutations, age, surgical stage and residual tumor — researchers observed a significant association between ADAMTS mutations and improved OS (HR = 0.53; 95% CI, 0.32-0.87), PFS (HR = 0.4; 95% CI, 0.25-0.62) and platinum-free survival (HR = 0.45; 95% CI, 0.28-0.73).
Researchers noted that patients who harbored ADAMTS mutations had a distinct mutation spectrum associated with a higher genome-wide mutation rate than wild-type patients (median mutation number, 121 vs. 69; P < .001).
“Using whole-exome sequencing, we have, for the first time to our knowledge, reported a novel association of ADAMTS mutations with longer survival and improved chemotherapy sensitivity in patients with ovarian cancer," Zhang and colleagues concluded. “The finding has important implications for clinical prediction and trial design and may be a useful addition to BRCA mutation assessment for patients with ovarian cancer.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
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