Nature Communications (Nov 2024)
Genomic and transcriptomic landscape of human gastrointestinal stromal tumors
- 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
Affiliations
- Feifei Xie
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Shuzhen Luo
- Institute of Intelligent Medical Research (IIMR), BGI Genomics
- Dongbing Liu
- Institute of Intelligent Medical Research (IIMR), BGI Genomics
- Xiaojing Lu
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Ming Wang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
- Xiaoxiao Liu
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Fujian Jia
- Guangdong Provincial Key Laboratory of Human Disease Genomics, BGI Research
- Yuzhi Pang
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Yanying Shen
- Department of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
- Chunling Zeng
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Xinli Ma
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
- Daoqiang Tang
- Department of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
- Lin Tu
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
- Linxi Yang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
- Yumei Cheng
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Yuxiang Luo
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Fanfan Xie
- Guangdong Provincial Key Laboratory of Human Disease Genomics, BGI Research
- Hao Hou
- Guangdong Provincial Key Laboratory of Human Disease Genomics, BGI Research
- Tao Huang
- Bioinformatics Core, Shanghai Institute of Nutrition and Health
- Bo Ni
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
- Chun Zhuang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
- Wenyi Zhao
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
- Ke Li
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Xufen Zheng
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Wenbo Bi
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Xiaona Jia
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Yi He
- Department of Urology, No.1 Hospital of Jiaxing
- Simin Wang
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Hui Cao
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
- Kui Wu
- Institute of Intelligent Medical Research (IIMR), BGI Genomics
- Yuexiang Wang
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- DOI
- https://doi.org/10.1038/s41467-024-53821-1
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 20
Abstract
Abstract Gastrointestinal stromal tumor (GISTs) are clinically heterogenous exhibiting varying degrees of disease aggressiveness in individual patients. We comprehensively describe the genomic and transcriptomic landscape of a cohort of 117 GISTs including 31 low-risk, 18 intermediate-risk, 29 high-risk, 34 metastatic and 5 neoadjuvant GISTs from 105 patients. GISTs have notably low tumor mutation burden but widespread copy number variations. Aggressive GISTs harbor remarkably more genomic aberrations than low-/intermediate-risk GISTs. Complex genomic alterations, chromothripsis and kataegis, occur selectively in aggressive GISTs. Despite the paucity of mutations, recurrent inactivating YLPM1 mutations are identified (10.3%, 7 of 68 patients), enriched in high-risk/metastatic GIST and functional study further demonstrates YLPM1 inactivation promotes GIST proliferation, growth and oxidative phosphorylation. Spatially and temporally separated GISTs from individual patients demonstrate complex tumor heterogeneity in metastatic GISTs. Finally, four prominent subtypes are proposed with different genomic features, expression profiles, immune characteristics, clinical characteristics and subtype-specific treatment strategies. This large-scale analysis depicts the landscape and provides further insights into GIST pathogenesis and precise treatment.
