Germline mutations in cancer-predisposition genes in patients with biliary tract cancer
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Takeshi Terashima1,2, Kumiko Umemoto3, Hideaki Takahashi3, Hiroko Hosoi2, Erina Takai4, Shunsuke Kondo2, Yasunari Sakamoto2, Shuichi Mitsunaga3, Izumi Ohno3, Yusuke Hashimoto3, Mitsuhito Sasaki3, Masafumi Ikeda3, Kazuaki Shimada5, Shuichi Kaneko1, Shinichi Yachida4, Kokichi Sugano6,7, Takuji Okusaka2 and Chigusa Morizane2
1 Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
2 Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
3 Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
4 Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
5 Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan
6 Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Tochigi, Japan
7 Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan
Keywords: germline mutations; biliary tract cancer; hereditary breast cancer syndrome; hereditary ovarian cancer syndrome; cancer-predisposition genes
Received: July 22, 2019 Accepted: September 10, 2019 Published: October 15, 2019
The prevalence of germline mutations in patients with biliary tract carcinoma (BTC) remains unclear. Here, we investigated the prevalence and types of germline mutations in patients with BTC. We reviewed 269 patients with pathologically proven BTC and collected clinical characteristics, including medical and family histories. Additionally, we evaluated germline variants in 21 genes associated with hereditary predisposition for cancer by targeted sequencing in patients meeting ≥1 of the following criteria: 1) hereditary breast and/or ovarian cancer (HBOC) testing criteria modified for BTC, 2) Revised Bethesda Guidelines (RBGs) modified for BTC (modified RBG), 3) familial BTC criteria, or 4) young BTC criteria. Among the 269 patients, 80 met at least one criterion. Three pathogenic mutations in three patients were identified: two in BRCA2 and one in BRCA1. Among the 16 patients meeting modified HBOC testing criteria, 2 harbored germline BRCA2 mutations, and 1 harbored a germline BRCA1 mutation. However, no mutation in mismatch-repair genes were detected, despite 63 patients meeting modified RBG screening criteria and 18 qualifying as young BTC patients. We detected high prevalence of pathogenic germline mutations in BRCA1/2 and none in mismatch-repair genes in BTC patients following enrichment according to family or medical history in this study.
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