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CC BY 4.0 · Glob Med Genet 2024; 11(04): 251-262
DOI: 10.1055/s-0044-1789204
Review Article

Gene Mutations in Gastrointestinal Stromal Tumors: Advances in Treatment and Mechanism Research

Lei Cao   *
1   Department of General Surgery, Tianjin Union Medical Center, Tianjin, People's Republic of China
2   Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center, Tianjin, People's Republic of China
,
Wencong Tian   *
1   Department of General Surgery, Tianjin Union Medical Center, Tianjin, People's Republic of China
,
Yongjie Zhao
1   Department of General Surgery, Tianjin Union Medical Center, Tianjin, People's Republic of China
2   Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center, Tianjin, People's Republic of China
,
Peng Song
1   Department of General Surgery, Tianjin Union Medical Center, Tianjin, People's Republic of China
,
Jia Zhao
1   Department of General Surgery, Tianjin Union Medical Center, Tianjin, People's Republic of China
,
Chuntao Wang
1   Department of General Surgery, Tianjin Union Medical Center, Tianjin, People's Republic of China
,
Yanhong Liu
1   Department of General Surgery, Tianjin Union Medical Center, Tianjin, People's Republic of China
,
Hong Fang
1   Department of General Surgery, Tianjin Union Medical Center, Tianjin, People's Republic of China
,
Xingqiang Liu
1   Department of General Surgery, Tianjin Union Medical Center, Tianjin, People's Republic of China
› Author Affiliations
Funding This work was supported by the Tianjin Medical Key Discipline (Specialty) Construction Project (TJYXZDXK-058B) and the Tianjin Health Research Project (TJWJ2023XK014).
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Abstract

Although gastrointestinal stromal tumors (GISTs) has been reported in patients of all ages, its diagnosis is more common in elders. The two most common types of mutation, receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor a (PDGFRA) mutations, hold about 75 and 15% of GISTs cases, respectively. Tumors without KIT or PDGFRA mutations are known as wild type (WT)-GISTs, which takes up for 15% of all cases. WT-GISTs have other genetic alterations, including mutations of the succinate dehydrogenase and serine–threonine protein kinase BRAF and neurofibromatosis type 1. Other GISTs without any of the above genetic mutations are named “quadruple WT” GISTs. More types of rare mutations are being reported. These mutations or gene fusions were initially thought to be mutually exclusive in primary GISTs, but recently it has been reported that some of these rare mutations coexist with KIT or PDGFRA mutations. The treatment and management differ according to molecular subtypes of GISTs. Especially for patients with late-stage tumors, developing a personalized chemotherapy regimen based on mutation status is of great help to improve patient survival and quality of life. At present, imatinib mesylate is an effective first-line drug for the treatment of unresectable or metastatic recurrent GISTs, but how to overcome drug resistance is still an important clinical problem. The effectiveness of other drugs is being further evaluated. The progress in the study of relevant mechanisms also provides the possibility to develop new targets or new drugs.

Keywords

GISTs - gene mutation - molecular mechanism - targeted therapies - drug resistance

* Lei Cao and Wencong Tian contributed equally to this work.




Publication History

Article published online:
22 August 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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