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Germline Cancer Susceptibility Gene Testing in Unselected Patients with Hepatobiliary Cancers: A Multi-Center Prospective Study
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for Cancer Research
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662853/ https://www.ncbi.nlm.nih.gov/pubmed/34782326 http://dx.doi.org/10.1158/1940-6207.CAPR-21-0189 |
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author | Uson Junior, Pedro LS Kunze, Katie L. Golafshar, Michael A. Riegert-Johnson, Douglas Boardman, Lisa Borad, Mitesh J. Ahn, Daniel Sonbol, Mohamad B. Faigel, Douglas O. Fukami, Norio Pannala, Rahul Barrus, Kathleen Mountjoy, Luke Esplin, Edward D. Nussbaum, Robert L. Stewart, A. Keith Bekaii-Saab, Tanios Samadder, N. Jewel |
author_facet | Uson Junior, Pedro LS Kunze, Katie L. Golafshar, Michael A. Riegert-Johnson, Douglas Boardman, Lisa Borad, Mitesh J. Ahn, Daniel Sonbol, Mohamad B. Faigel, Douglas O. Fukami, Norio Pannala, Rahul Barrus, Kathleen Mountjoy, Luke Esplin, Edward D. Nussbaum, Robert L. Stewart, A. Keith Bekaii-Saab, Tanios Samadder, N. Jewel |
author_sort | Uson Junior, Pedro LS |
collection | PubMed |
description | 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% (n = 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. |
format | Online Article Text |
id | pubmed-9662853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for Cancer Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-96628532023-01-05 Germline Cancer Susceptibility Gene Testing in Unselected Patients with Hepatobiliary Cancers: A Multi-Center Prospective Study Uson Junior, Pedro LS Kunze, Katie L. Golafshar, Michael A. Riegert-Johnson, Douglas Boardman, Lisa Borad, Mitesh J. Ahn, Daniel Sonbol, Mohamad B. Faigel, Douglas O. Fukami, Norio Pannala, Rahul Barrus, Kathleen Mountjoy, Luke Esplin, Edward D. Nussbaum, Robert L. Stewart, A. Keith Bekaii-Saab, Tanios Samadder, N. Jewel Cancer Prev Res (Phila) Research Articles 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% (n = 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. American Association for Cancer Research 2022-02-01 2021-11-15 /pmc/articles/PMC9662853/ /pubmed/34782326 http://dx.doi.org/10.1158/1940-6207.CAPR-21-0189 Text en ©2021 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
spellingShingle | Research Articles Uson Junior, Pedro LS Kunze, Katie L. Golafshar, Michael A. Riegert-Johnson, Douglas Boardman, Lisa Borad, Mitesh J. Ahn, Daniel Sonbol, Mohamad B. Faigel, Douglas O. Fukami, Norio Pannala, Rahul Barrus, Kathleen Mountjoy, Luke Esplin, Edward D. Nussbaum, Robert L. Stewart, A. Keith Bekaii-Saab, Tanios Samadder, N. Jewel Germline Cancer Susceptibility Gene Testing in Unselected Patients with Hepatobiliary Cancers: A Multi-Center Prospective Study |
title | Germline Cancer Susceptibility Gene Testing in Unselected Patients with Hepatobiliary Cancers: A Multi-Center Prospective Study |
title_full | Germline Cancer Susceptibility Gene Testing in Unselected Patients with Hepatobiliary Cancers: A Multi-Center Prospective Study |
title_fullStr | Germline Cancer Susceptibility Gene Testing in Unselected Patients with Hepatobiliary Cancers: A Multi-Center Prospective Study |
title_full_unstemmed | Germline Cancer Susceptibility Gene Testing in Unselected Patients with Hepatobiliary Cancers: A Multi-Center Prospective Study |
title_short | Germline Cancer Susceptibility Gene Testing in Unselected Patients with Hepatobiliary Cancers: A Multi-Center Prospective Study |
title_sort | germline cancer susceptibility gene testing in unselected patients with hepatobiliary cancers: a multi-center prospective study |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662853/ https://www.ncbi.nlm.nih.gov/pubmed/34782326 http://dx.doi.org/10.1158/1940-6207.CAPR-21-0189 |
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