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Expanded genetic testing of GIST patients identifies high proportion of non-syndromic patients with germline alterations
Traditional genetic testing for patients with gastrointestinal stromal tumors (GISTs) focus on those with syndromic features. To assess whether expanded genetic testing of GIST patients could identify hereditary cancer predisposition, we analyzed matched tumor-germline sequencing results from 103 pa...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807588/ https://www.ncbi.nlm.nih.gov/pubmed/36593350 http://dx.doi.org/10.1038/s41698-022-00342-z |
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author | Mandelker, Diana Marra, Antonio Mehta, Nikita Selenica, Pier Yelskaya, Zarina Yang, Ciyu Somar, Joshua Mehine, Miika Misyura, Maksym Basturk, Olca Latham, Alicia Carlo, Maria Walsh, Michael Stadler, Zsofia K. Offit, Kenneth Bandlamudi, Chaitanya Hameed, Meera Chi, Ping Reis-Filho, Jorge S. Ceyhan-Birsoy, Ozge |
author_facet | Mandelker, Diana Marra, Antonio Mehta, Nikita Selenica, Pier Yelskaya, Zarina Yang, Ciyu Somar, Joshua Mehine, Miika Misyura, Maksym Basturk, Olca Latham, Alicia Carlo, Maria Walsh, Michael Stadler, Zsofia K. Offit, Kenneth Bandlamudi, Chaitanya Hameed, Meera Chi, Ping Reis-Filho, Jorge S. Ceyhan-Birsoy, Ozge |
author_sort | Mandelker, Diana |
collection | PubMed |
description | Traditional genetic testing for patients with gastrointestinal stromal tumors (GISTs) focus on those with syndromic features. To assess whether expanded genetic testing of GIST patients could identify hereditary cancer predisposition, we analyzed matched tumor-germline sequencing results from 103 patients with GISTs over a 6-year period. Germline pathogenic/likely pathogenic (P/LP) variants in GIST-associated genes (SDHA, SDHB, SDHC, NF1, KIT) were identified in 69% of patients with KIT/PDGFRA-wildtype GISTs, 63% of whom did not have any personal or family history of syndromic features. To evaluate the frequency of somatic versus germline variants identified in tumor-only sequencing of GISTs, we analyzed 499 de-identified tumor-normal pairs. P/LP variants in certain genes (e.g., BRCA1/2, SDHB) identified in tumor-only sequencing of GISTs were almost exclusively germline in origin. Our results provide guidance for genetic testing of GIST patients and indicate that germline testing should be offered to all patients with KIT/PDGFRA-wildtype GISTs regardless of their history of syndromic features. |
format | Online Article Text |
id | pubmed-9807588 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98075882023-01-04 Expanded genetic testing of GIST patients identifies high proportion of non-syndromic patients with germline alterations Mandelker, Diana Marra, Antonio Mehta, Nikita Selenica, Pier Yelskaya, Zarina Yang, Ciyu Somar, Joshua Mehine, Miika Misyura, Maksym Basturk, Olca Latham, Alicia Carlo, Maria Walsh, Michael Stadler, Zsofia K. Offit, Kenneth Bandlamudi, Chaitanya Hameed, Meera Chi, Ping Reis-Filho, Jorge S. Ceyhan-Birsoy, Ozge NPJ Precis Oncol Brief Communication Traditional genetic testing for patients with gastrointestinal stromal tumors (GISTs) focus on those with syndromic features. To assess whether expanded genetic testing of GIST patients could identify hereditary cancer predisposition, we analyzed matched tumor-germline sequencing results from 103 patients with GISTs over a 6-year period. Germline pathogenic/likely pathogenic (P/LP) variants in GIST-associated genes (SDHA, SDHB, SDHC, NF1, KIT) were identified in 69% of patients with KIT/PDGFRA-wildtype GISTs, 63% of whom did not have any personal or family history of syndromic features. To evaluate the frequency of somatic versus germline variants identified in tumor-only sequencing of GISTs, we analyzed 499 de-identified tumor-normal pairs. P/LP variants in certain genes (e.g., BRCA1/2, SDHB) identified in tumor-only sequencing of GISTs were almost exclusively germline in origin. Our results provide guidance for genetic testing of GIST patients and indicate that germline testing should be offered to all patients with KIT/PDGFRA-wildtype GISTs regardless of their history of syndromic features. Nature Publishing Group UK 2023-01-02 /pmc/articles/PMC9807588/ /pubmed/36593350 http://dx.doi.org/10.1038/s41698-022-00342-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Brief Communication Mandelker, Diana Marra, Antonio Mehta, Nikita Selenica, Pier Yelskaya, Zarina Yang, Ciyu Somar, Joshua Mehine, Miika Misyura, Maksym Basturk, Olca Latham, Alicia Carlo, Maria Walsh, Michael Stadler, Zsofia K. Offit, Kenneth Bandlamudi, Chaitanya Hameed, Meera Chi, Ping Reis-Filho, Jorge S. Ceyhan-Birsoy, Ozge Expanded genetic testing of GIST patients identifies high proportion of non-syndromic patients with germline alterations |
title | Expanded genetic testing of GIST patients identifies high proportion of non-syndromic patients with germline alterations |
title_full | Expanded genetic testing of GIST patients identifies high proportion of non-syndromic patients with germline alterations |
title_fullStr | Expanded genetic testing of GIST patients identifies high proportion of non-syndromic patients with germline alterations |
title_full_unstemmed | Expanded genetic testing of GIST patients identifies high proportion of non-syndromic patients with germline alterations |
title_short | Expanded genetic testing of GIST patients identifies high proportion of non-syndromic patients with germline alterations |
title_sort | expanded genetic testing of gist patients identifies high proportion of non-syndromic patients with germline alterations |
topic | Brief Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807588/ https://www.ncbi.nlm.nih.gov/pubmed/36593350 http://dx.doi.org/10.1038/s41698-022-00342-z |
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