Genomic and transcriptomic landscape of human gastrointestinal stromal tumors
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.
Authors
- Wenyi Zhao (ORCID: https://orcid.org/0000-0002-8339-5081)
- Simin Wang (ORCID: https://orcid.org/0000-0001-6135-7546)
- Bo Ni (ORCID: https://orcid.org/0000-0001-9154-1213)
- Chunling Zeng (ORCID: https://orcid.org/0000-0003-2575-5613)
- Hao Hou
- Tao Huang (ORCID: https://orcid.org/0000-0003-1975-9693)
- Kui Wu (ORCID: https://orcid.org/0000-0002-6857-7231)
- Feifei Xie (ORCID: https://orcid.org/0000-0001-9926-2809)
- Dongbing Liu (ORCID: https://orcid.org/0000-0003-2870-5187)
- Xufen Zheng (ORCID: https://orcid.org/0000-0002-0081-8676)
- Fujian Jia
- Yi He (ORCID: https://orcid.org/0000-0002-1752-8405)
- Lin Tu (ORCID: https://orcid.org/0000-0001-6012-9285)
- Yumei Cheng (ORCID: https://orcid.org/0000-0003-4697-3599)
- Fanfan Xie (ORCID: https://orcid.org/0000-0002-0593-2347)
- Daoqiang Tang
- Xiaoxiao Liu (ORCID: https://orcid.org/0000-0001-5582-9084)
- Ke Li (ORCID: https://orcid.org/0000-0003-2671-926X)
- Ming Wang (ORCID: https://orcid.org/0000-0002-7000-1063)
- Xiaona Jia (ORCID: https://orcid.org/0000-0001-9823-9658)
- Yuexiang Wang (ORCID: https://orcid.org/0000-0003-3229-5467)
- Xinli Ma
- Yanying Shen (ORCID: https://orcid.org/0000-0001-9195-2207)
- Xiaojing Lu (ORCID: https://orcid.org/0000-0001-7628-7245)
- Hui Cao (ORCID: https://orcid.org/0000-0002-5901-5499)
- Linxi Yang
- Yuzhi Pang (ORCID: https://orcid.org/0000-0003-0713-8320)
- Wenbo Bi (ORCID: https://orcid.org/0000-0002-5150-4220)
- Chun Zhuang (ORCID: https://orcid.org/0000-0001-8127-4510)
- Yuxiang Luo
- Shuzhen Luo
Institutions
- BGI Group (China) (CN)
- Shanghai Jiao Tong University (CN)
- Renji Hospital (CN)
- Shanghai Institute of Nutrition and Health (CN)
- International Peace Maternity & Child Health Hospital (CN)
- First Hospital of Jiaxing (CN)
- University of Chinese Academy of Sciences (CN)
- BGI Genomics
- BGI Research (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-03
- DOI
- https://doi.org/10.1038/s41467-024-53821-1
- Citations
- 18
- Primary Topic
- Gastrointestinal Tumor Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 8.35
Funders
- Brigham and Women's Hospital