BACKGROUND: With limited information on germline mutations in biliary tract cancers, this study performed somatic and germline testing for patients at Memorial Sloan Kettering Cancer Center with known biliary tract carcinoma with the aim of determining the frequency and range of pathogenic germline alterations (PGAs). METHODS: Patients with biliary tract carcinoma were consented for somatic tumor and matched blood testing of up to 468 genes via the Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets next-generation sequencing platform. A germline variant analysis was performed on a panel of up to 88 genes associated with an increased predisposition for cancer. Demographic and diagnostic details were collected. RESULTS: Germline mutations were tested in 131 patients. Intrahepatic cholangiocarcinoma was the most common cancer (63.4%), and it was followed by gallbladder adenocarcinoma (16.8%), extrahepatic cholangiocarcinoma (16%), and otherwise unspecified biliary tract cancer (3.8%). Known and likely PGAs were present in 21 patients (16.0%), with 9.9% harboring a PGA in a high/moderate-penetrance cancer predisposition gene. Among high-penetrance cancer susceptibility genes, PGAs were most commonly observed in BRCA1 and BRCA2 (33.3%), which made up 5.3% of the entire cohort, and they were followed by PALB2, BAP1, and PMS2. Mutations in ATM, MITF, and NBN, moderate-penetrance cancer susceptibility genes, were identified in 1 patient each. There was no observed difference in the types of mutations among the subtypes of biliary tract cancer. CONCLUSIONS: The frequency of PGAs found was comparable to existing data on the prevalence of germline mutations in other solid tumor types with matched tumor analysis. This provides support for the role of the BRCA1/2, ATM, and BAP1 genes in biliary tract cancer susceptibility.
BACKGROUND: With limited information on germline mutations in biliary tract cancers, this study performed somatic and germline testing for patients at Memorial Sloan Kettering Cancer Center with known biliary tract carcinoma with the aim of determining the frequency and range of pathogenic germline alterations (PGAs). METHODS:Patients with biliary tract carcinoma were consented for somatic tumor and matched blood testing of up to 468 genes via the Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets next-generation sequencing platform. A germline variant analysis was performed on a panel of up to 88 genes associated with an increased predisposition for cancer. Demographic and diagnostic details were collected. RESULTS: Germline mutations were tested in 131 patients. Intrahepatic cholangiocarcinoma was the most common cancer (63.4%), and it was followed by gallbladder adenocarcinoma (16.8%), extrahepatic cholangiocarcinoma (16%), and otherwise unspecifiedbiliary tract cancer (3.8%). Known and likely PGAs were present in 21 patients (16.0%), with 9.9% harboring a PGA in a high/moderate-penetrance cancer predisposition gene. Among high-penetrance cancer susceptibility genes, PGAs were most commonly observed in BRCA1 and BRCA2 (33.3%), which made up 5.3% of the entire cohort, and they were followed by PALB2, BAP1, and PMS2. Mutations in ATM, MITF, and NBN, moderate-penetrance cancer susceptibility genes, were identified in 1 patient each. There was no observed difference in the types of mutations among the subtypes of biliary tract cancer. CONCLUSIONS: The frequency of PGAs found was comparable to existing data on the prevalence of germline mutations in other solid tumor types with matched tumor analysis. This provides support for the role of the BRCA1/2, ATM, and BAP1 genes in biliary tract cancer susceptibility.
Authors: Milind Javle; Maeve Lowery; Rachna T Shroff; Karl Heinz Weiss; Christoph Springfeld; Mitesh J Borad; Ramesh K Ramanathan; Lipika Goyal; Saeed Sadeghi; Teresa Macarulla; Anthony El-Khoueiry; Robin Kate Kelley; Ivan Borbath; Su Pin Choo; Do-Youn Oh; Philip A Philip; Li-Tzong Chen; Thanyanan Reungwetwattana; Eric Van Cutsem; Kun-Huei Yeh; Kristen Ciombor; Richard S Finn; Anuradha Patel; Suman Sen; Dale Porter; Randi Isaacs; Andrew X Zhu; Ghassan K Abou-Alfa; Tanios Bekaii-Saab Journal: J Clin Oncol Date: 2017-11-28 Impact factor: 44.544
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Authors: Robert Pilarski; Colleen M Cebulla; James B Massengill; Karan Rai; Thereasa Rich; Louise Strong; Barbara McGillivray; Mary-Jill Asrat; Frederick H Davidorf; Mohamed H Abdel-Rahman Journal: Genes Chromosomes Cancer Date: 2013-11-15 Impact factor: 5.006
Authors: Darrell R Borger; Kenneth K Tanabe; Kenneth C Fan; Hector U Lopez; Valeria R Fantin; Kimberly S Straley; David P Schenkein; Aram F Hezel; Marek Ancukiewicz; Hannah M Liebman; Eunice L Kwak; Jeffrey W Clark; David P Ryan; Vikram Deshpande; Dora Dias-Santagata; Leif W Ellisen; Andrew X Zhu; A John Iafrate Journal: Oncologist Date: 2011-12-16 Impact factor: 5.837
Authors: Robert Power; Cristin Leavy; Carmel Nolan; Niamh White; Roisin Clarke; Karen A Cadoo; David James Gallagher; Maeve Aine Lowery Journal: Fam Cancer Date: 2020-09-12 Impact factor: 2.375