Genomic and transcriptomic landscape of human gastrointestinal stromal tumors

• DOI: 10.1038/s41467-024-53821-1
• Publication Date: 2024-11-03T07:02:19Z
• Authors: Feifei Xie; Shuzhen Luo; Dongbing Liu; Xiaojing Lu; Ming Wang; Xiaoxiao Liu; Fujian Jia; Yuzhi Pang; Yanying Shen; Chunling Zeng; Xinli Ma; Daoqiang Tang; Lin Tu; Linxi Yang; Yumei Cheng; Yuxiang Luo; Fanfan Xie; Hao Hou; Tao Huang; Bo Ni; Chun Zhuang; Wenyi Zhao; Ke Li; Xufen Zheng; Wenbo Bi; Xiaona Jia; Yi He; Simin Wang; Hui Cao; Kui Wu; Yuexiang Wang
• Keywords: Male; Adult; 0303 health sciences; DNA Copy Number Variations; Gastrointestinal Stromal Tumors; Science; Gene Expression Profiling; Q; Genomics; Middle Aged; Article; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Mutation; Humans; Female; Transcriptome; Aged; Gastrointestinal Neoplasms; Cell Proliferation

Gastrointestinal stromal tumor (GISTs) are clinically heterogenous exhibiting varying degrees of disease aggressiveness in individual patients. We comprehensively describe the genomic and transcriptomic landscape a cohort 117 GISTs including 31 low-risk, 18 intermediate-risk, 29 high-risk, 34 metastatic 5 neoadjuvant from 105 have notably low mutation burden but widespread copy number variations. Aggressive harbor remarkably more aberrations than low-/intermediate-risk GISTs. Complex alterations, chromothripsis kataegis, occur selectively aggressive Despite paucity mutations, recurrent inactivating YLPM1 mutations identified (10.3%, 7 68 patients), enriched high-risk/metastatic GIST functional study further demonstrates inactivation promotes proliferation, growth oxidative phosphorylation. Spatially temporally separated patients demonstrate complex heterogeneity Finally, four prominent subtypes proposed with different features, expression profiles, immune characteristics, clinical characteristics subtype-specific treatment strategies. This large-scale analysis depicts provides insights into pathogenesis precise treatment. tumours heterogeneous, aggressiveness. Here, authors patients; they find molecular as well GIST.