Expanded genetic testing of GIST patients identifies high proportion of non-syndromic patients with germline alterations.

Autor: Mandelker D; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Marra A; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Mehta N; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Selenica P; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Yelskaya Z; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Yang C; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Somar J; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Mehine M; Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Misyura M; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Basturk O; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Latham A; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Carlo M; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Walsh M; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Stadler ZK; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Offit K; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Bandlamudi C; Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hameed M; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Chi P; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Reis-Filho JS; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. reisfilj@mskcc.org., Ceyhan-Birsoy O; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. birsoyo@mskcc.org.
Jazyk: angličtina
Zdroj: NPJ precision oncology [NPJ Precis Oncol] 2023 Jan 02; Vol. 7 (1), pp. 1. Date of Electronic Publication: 2023 Jan 02.
DOI: 10.1038/s41698-022-00342-z
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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