Division of Hematology and Medical Oncology, Department of Medicine, Mayo Clinic, Phoenix, Arizona.
Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Phoenix, Arizona.
Cancer Prev Res (Phila). 2022 Feb;15(2):121-128. doi: 10.1158/1940-6207.CAPR-21-0189. Epub 2021 Nov 15.
Data from germline testing in unselected patients with hepatobiliary cancers are limited. Identification of germline predisposition can have important implications on cancer treatment and family counseling. To determine prevalence of pathogenic germline variants (PGV) in patients with hepatobiliary cancer, we undertook a prospective multi-site study of germline sequencing using a >80-gene next-generation sequencing platform among patients with hepatobiliary cancers receiving care at Mayo Clinic Cancer Centers between April 1, 2018 and March 31, 2020. Patients were not selected on the basis of stage, family cancer history, ethnicity, or age. Family cascade testing was offered at no cost. Of 205 patients, the median age was 65 years, 58.5% were male, 81% were White, and 64.4% had cholangiocarcinoma, 21.5% hepatocellular carcinoma, 7.8% gallbladder cancer, and 4.3% carcinoma of ampulla of Vater. PGV were found in 15.6% ( = 32) of patients, including 23 (71%) in moderate and high penetrance cancer susceptibility genes. A total of 75% of patients with a positive result would not have been detected using guidelines for genetic evaluation. Prevalence of PGV was 15.7% in intrahepatic cholangiocarcinoma, 17% in extrahepatic cholangiocarcinoma, 15.9% in hepatocellular cancer, and 33% in carcinoma of ampulla of Vater. On the basis of these genetic findings, 55% were potentially eligible for approved precision therapy and/or clinical treatment trials. Universal multi-gene panel testing in hepatobiliary cancers was associated with detection of heritable mutations in over 15% of patients most of whom would not have been tested using current guidelines. Germline testing should be considered in all patients with hepatobiliary cancers. PREVENTION RELEVANCE: Universal multi-gene testing in hepatobiliary cancers was associated with heritable mutations in over 15% of patients, most of whom would not have been tested using current guidelines. 55% were potentially eligible for approved precision therapy and/or clinical treatment trials. Germline testing should be considered in all patients with hepatobiliary cancers.
从未经选择的肝胆癌患者的种系检测中获得的数据有限。确定种系易感性是否存在可以对癌症治疗和家族咨询产生重要影响。为了确定肝胆癌患者中致病性种系变异（PGV）的患病率，我们在 2018 年 4 月 1 日至 2020 年 3 月 31 日期间，在梅奥诊所癌症中心接受治疗的肝胆癌患者中，使用 >80 个基因的下一代测序平台进行了前瞻性多地点种系测序研究。患者未根据分期、家族癌症史、种族或年龄进行选择。免费提供家族级联检测。在 205 名患者中，中位年龄为 65 岁，58.5%为男性，81%为白人，64.4%为胆管癌，21.5%为肝细胞癌，7.8%为胆囊癌，4.3%为壶腹癌。在 15.6%（=32）的患者中发现了 PGV，其中 23 例（71%）为中高外显率癌症易感性基因。如果使用遗传评估指南，将有 75%的阳性结果患者无法被检测到。肝内胆管癌的 PGV 患病率为 15.7%，肝外胆管癌为 17%，肝细胞癌为 15.9%，壶腹癌为 33%。基于这些遗传发现，55%的患者有资格接受已批准的精准治疗和/或临床治疗试验。肝胆癌的通用多基因面板检测与超过 15%的患者中可遗传突变的检测相关，其中大多数患者如果使用当前指南，将无法进行检测。应考虑对所有肝胆癌患者进行种系检测。预防相关性：肝胆癌的通用多基因检测与超过 15%的患者的遗传突变相关，其中大多数患者如果使用当前指南，将无法进行检测。55%的患者有资格参加已批准的精准治疗和/或临床治疗试验。应考虑对所有肝胆癌患者进行种系检测。
Zotero 插件