Englander Institute for Precision Medicine

Novel structural variants that impact cell cycle genes are elucidated in metastatic gastrointestinal stromal tumors.

TitleNovel structural variants that impact cell cycle genes are elucidated in metastatic gastrointestinal stromal tumors.
Publication TypeJournal Article
Year of Publication2024
Authorsde la Mora JDelgado-, Assaad MAl, Quitian S, Levine MF, Deshpande A, Sigouros M, Manohar J, Medina-Martínez JS, Sboner A, Elemento O, Jessurun J, Hissong E, Mosquera JMiguel
JournalPathol Res Pract
Volume266
Pagination155782
Date Published2024 Dec 18
ISSN1618-0631
Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the digestive tract. Despite multiple therapeutic advances, patients with advanced disease frequently develop resistance to tyrosine kinase inhibitors (TKIs), and therefore represent a therapeutic challenge. We employed whole genome sequencing (WGS) on three metastatic GISTs refractory to various TKIs and explored a publicly available cohort of 499 GISTs. This study sheds light on the clinical importance of alterations in cell cycle genes such as cyclin-dependent kinase 2 A (CDKN2A), and cyclin-dependent kinase 2B (CDKN2B), their frequent alteration in metastatic GISTs and their potential role in tumor progression of this neoplasm. Likewise, new structural variations were identified in cyclin-dependent kinase 12 (CDK12). Whole genome profiling of metastatic GIST provides new insights to advance precision care of the disease, focusing on new therapeutic possibilities, especially for emerging targets such as CDK12.

DOI10.1016/j.prp.2024.155782
Alternate JournalPathol Res Pract
PubMed ID39708519

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