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Prevalence of Germline Findings Among Tumors From Cancer Types Lacking Hereditary Testing Guidelines

IMPORTANCE: Germline testing guidelines are suggested for specific disease types or a family history of cancer, yet alterations are found in cancer types in which germline testing is not routinely indicated. The clinical role of identifying germline variants in these populations is valuable to patie...

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Autores principales: Yap, Timothy A., Ashok, Arya, Stoll, Jessica, Mauer, Elizabeth, Nepomuceno, Vanessa M., Blackwell, Kimberly L., Garber, Judy E., Meric-Bernstam, Funda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123503/
https://www.ncbi.nlm.nih.gov/pubmed/35594047
http://dx.doi.org/10.1001/jamanetworkopen.2022.13070
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author Yap, Timothy A.
Ashok, Arya
Stoll, Jessica
Mauer, Elizabeth
Nepomuceno, Vanessa M.
Blackwell, Kimberly L.
Garber, Judy E.
Meric-Bernstam, Funda
author_facet Yap, Timothy A.
Ashok, Arya
Stoll, Jessica
Mauer, Elizabeth
Nepomuceno, Vanessa M.
Blackwell, Kimberly L.
Garber, Judy E.
Meric-Bernstam, Funda
author_sort Yap, Timothy A.
collection PubMed
description IMPORTANCE: Germline testing guidelines are suggested for specific disease types or a family history of cancer, yet alterations are found in cancer types in which germline testing is not routinely indicated. The clinical role of identifying germline variants in these populations is valuable to patients and their at-risk relatives. OBJECTIVE: To evaluate the prevalence of germline findings in patients undergoing tumor/normal matched sequencing among cancer types lacking guidelines. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study took place on August 18, 2021, and included data from deidentified records of patients tested, using the Tempus xT tumor/normal matched approach from November 2017 to August 2021. Records included in this study were from 34 642 patients treated in geographically diverse oncology practices in the US with a diagnosis of any of the following cancers: bladder, brain, lung, esophagus, cholangiocarcinoma, head and neck, breast, ovarian, pancreatic, prostate, endometrial, and colorectal. MAIN OUTCOMES AND MEASURES: The rate of germline findings (ie, single-nucleotide variants and small insertions or deletions) detected in 50 reportable hereditary cancer genes was calculated for cancer types lacking guidelines for germline testing (bladder, brain, lung, esophagus, cholangiocarcinoma, and head and neck) and cancer types for which germline testing is frequently performed (breast, ovarian, pancreatic, prostate, endometrial, and colorectal). Same-gene second somatic hits were assessed to provide a comprehensive assessment on genomic drivers. RESULTS: Of 34 642 patients, 18 888 were female (54.5%); of 27 498 patients whose age at diagnosis was known, mean (SD) age was 62.23 (3.36) years. A total of 2534 of 34 642 patients (7.3%) harbored pathogenic or likely pathogenic germline variants. Within the tumor types lacking testing guidelines, germline mutations were at 6.6% (79/1188) in bladder cancer and 5.8% (448/7668) in lung cancer. CONCLUSIONS AND RELEVANCE: This study may present the largest retrospective analysis to date of deidentified real-world data from patients diagnosed with advanced cancer with tumor/normal matched sequencing data and the prevalence of pathogenic or likely pathogenic germline variants in cancer types lacking hereditary cancer testing guidelines. The findings suggest there may be clinical implications for patients and their at-risk family members in cancers for which germline assessment primarily based on the cancer diagnosis is rarely obtained.
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spelling pubmed-91235032022-06-04 Prevalence of Germline Findings Among Tumors From Cancer Types Lacking Hereditary Testing Guidelines Yap, Timothy A. Ashok, Arya Stoll, Jessica Mauer, Elizabeth Nepomuceno, Vanessa M. Blackwell, Kimberly L. Garber, Judy E. Meric-Bernstam, Funda JAMA Netw Open Original Investigation IMPORTANCE: Germline testing guidelines are suggested for specific disease types or a family history of cancer, yet alterations are found in cancer types in which germline testing is not routinely indicated. The clinical role of identifying germline variants in these populations is valuable to patients and their at-risk relatives. OBJECTIVE: To evaluate the prevalence of germline findings in patients undergoing tumor/normal matched sequencing among cancer types lacking guidelines. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study took place on August 18, 2021, and included data from deidentified records of patients tested, using the Tempus xT tumor/normal matched approach from November 2017 to August 2021. Records included in this study were from 34 642 patients treated in geographically diverse oncology practices in the US with a diagnosis of any of the following cancers: bladder, brain, lung, esophagus, cholangiocarcinoma, head and neck, breast, ovarian, pancreatic, prostate, endometrial, and colorectal. MAIN OUTCOMES AND MEASURES: The rate of germline findings (ie, single-nucleotide variants and small insertions or deletions) detected in 50 reportable hereditary cancer genes was calculated for cancer types lacking guidelines for germline testing (bladder, brain, lung, esophagus, cholangiocarcinoma, and head and neck) and cancer types for which germline testing is frequently performed (breast, ovarian, pancreatic, prostate, endometrial, and colorectal). Same-gene second somatic hits were assessed to provide a comprehensive assessment on genomic drivers. RESULTS: Of 34 642 patients, 18 888 were female (54.5%); of 27 498 patients whose age at diagnosis was known, mean (SD) age was 62.23 (3.36) years. A total of 2534 of 34 642 patients (7.3%) harbored pathogenic or likely pathogenic germline variants. Within the tumor types lacking testing guidelines, germline mutations were at 6.6% (79/1188) in bladder cancer and 5.8% (448/7668) in lung cancer. CONCLUSIONS AND RELEVANCE: This study may present the largest retrospective analysis to date of deidentified real-world data from patients diagnosed with advanced cancer with tumor/normal matched sequencing data and the prevalence of pathogenic or likely pathogenic germline variants in cancer types lacking hereditary cancer testing guidelines. The findings suggest there may be clinical implications for patients and their at-risk family members in cancers for which germline assessment primarily based on the cancer diagnosis is rarely obtained. American Medical Association 2022-05-20 /pmc/articles/PMC9123503/ /pubmed/35594047 http://dx.doi.org/10.1001/jamanetworkopen.2022.13070 Text en Copyright 2022 Yap TA et al. JAMA Network Open. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the CC-BY-NC-ND License.
spellingShingle Original Investigation
Yap, Timothy A.
Ashok, Arya
Stoll, Jessica
Mauer, Elizabeth
Nepomuceno, Vanessa M.
Blackwell, Kimberly L.
Garber, Judy E.
Meric-Bernstam, Funda
Prevalence of Germline Findings Among Tumors From Cancer Types Lacking Hereditary Testing Guidelines
title Prevalence of Germline Findings Among Tumors From Cancer Types Lacking Hereditary Testing Guidelines
title_full Prevalence of Germline Findings Among Tumors From Cancer Types Lacking Hereditary Testing Guidelines
title_fullStr Prevalence of Germline Findings Among Tumors From Cancer Types Lacking Hereditary Testing Guidelines
title_full_unstemmed Prevalence of Germline Findings Among Tumors From Cancer Types Lacking Hereditary Testing Guidelines
title_short Prevalence of Germline Findings Among Tumors From Cancer Types Lacking Hereditary Testing Guidelines
title_sort prevalence of germline findings among tumors from cancer types lacking hereditary testing guidelines
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123503/
https://www.ncbi.nlm.nih.gov/pubmed/35594047
http://dx.doi.org/10.1001/jamanetworkopen.2022.13070
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