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

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

Authors:	Mandelker, D.; Marra, A.; Mehta, N.; Selenica, P.; Yelskaya, Z.; Yang, C.; Somar, J.; Mehine, M.; Misyura, M.; Basturk, O.; Latham, A.; Carlo, M.; Walsh, M.; Stadler, Z. K.; Offit, K.; Bandlamudi, C.; Hameed, M.; Chi, P.; Reis-Filho, J. S.; Ceyhan-Birsoy, O.
Article Title:	Expanded genetic testing of GIST patients identifies high proportion of non-syndromic patients with germline alterations
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. © 2022, The Author(s).
Keywords:	immunohistochemistry; adult; controlled study; human tissue; human cell; major clinical study; promoter region; single nucleotide polymorphism; somatic mutation; allele; gastrointestinal stromal tumor; stem cell factor receptor; cancer susceptibility; metastasis; clinical assessment; cohort analysis; brca1 protein; brca2 protein; haplotype; microsatellite instability; family history; population; neurofibromin; heterozygosity loss; genetic screening; genomic dna; succinate dehydrogenase; germline mutation; high throughput sequencing; dna sequencing; human; article; hereditary tumor syndrome
Journal Title:	npj Precision Oncology
Volume:	7
ISSN:	2397-768X
Publisher:	Springer Nature
Date Published:	2023-01-02
Start Page:	1
Language:	English
DOI:	10.1038/s41698-022-00342-z
PROVIDER:	scopus
PMCID:	PMC9807588
PUBMED:	36593350
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85145414388&doi=10.1038%2fs41698-022-00342-z&partnerID=40&md5=f4cfe505f2767bf9d4d3d0632abd0911
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding authors are Jorge S. Reis-Filho and Ozge Ceyhan-Birsoy -- Export Date: 1 February 2023 -- Source: Scopus