학술논문
Expanded genetic testing of GIST patients identifies high proportion of non-syndromic patients with germline alterations
Document Type
article
Author
Diana Mandelker; Antonio Marra; Nikita Mehta; Pier Selenica; Zarina Yelskaya; Ciyu Yang; Joshua Somar; Miika Mehine; Maksym Misyura; Olca Basturk; Alicia Latham; Maria Carlo; Michael Walsh; Zsofia K. Stadler; Kenneth Offit; Chaitanya Bandlamudi; Meera Hameed; Ping Chi; Jorge S. Reis-Filho; Ozge Ceyhan-Birsoy
Source
npj Precision Oncology, Vol 7, Iss 1, Pp 1-6 (2023)
Subject
Language
English
ISSN
2397-768X
Abstract
Abstract 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.