Genomic landscape and immunological profile of glioblastoma in East Asian patients

Sheng Zhong; Bo Wu; Frank Dubois; Davy Deng; Johann S Bergholz; Wanming Hu; Hao Duan; Yujie Shao; Jingyi Liu; Luwei Liu; Sitong Chen; Yongfei Hu; Zheng Zhao; Maojin Yao; Ke Sai; Jian Wang; Yinsheng Chen; Chao Ke; Xiangheng Zhang; Qunying Yang; Chengcheng Guo; Ji Zhang; Fuhua Lin; Zhenghe Chen; Deipei Li; Zhenqiang He; Chang Li; Xiaobing Jiang; Jie Lu; Wenzhuo Yang; Tao Jiang; Zhongping Chen; Rameen Beroukhim; Jean J Zhao; Yonggao Mou

doi:10.1016/j.xcrm.2025.102217

Genomic landscape and immunological profile of glioblastoma in East Asian patients

Cell Rep Med. 2025 Aug 19;6(8):102217. doi: 10.1016/j.xcrm.2025.102217.

Authors

Sheng Zhong¹, Bo Wu², Frank Dubois³, Davy Deng⁴, Johann S Bergholz⁵, Wanming Hu⁶, Hao Duan⁷, Yujie Shao⁸, Jingyi Liu⁸, Luwei Liu⁸, Sitong Chen⁸, Yongfei Hu⁷, Zheng Zhao⁹, Maojin Yao¹⁰, Ke Sai⁷, Jian Wang⁷, Yinsheng Chen⁷, Chao Ke⁷, Xiangheng Zhang⁷, Qunying Yang⁷, Chengcheng Guo⁷, Ji Zhang⁷, Fuhua Lin⁷, Zhenghe Chen⁷, Deipei Li⁷, Zhenqiang He⁷, Chang Li⁷, Xiaobing Jiang⁷, Jie Lu⁷, Wenzhuo Yang⁷, Tao Jiang¹¹, Zhongping Chen¹², Rameen Beroukhim¹³, Jean J Zhao¹⁴, Yonggao Mou¹⁵

Affiliations

¹ Department of Neurosurgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
² Lower Extremity Division, Orthopedic Trauma Department, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
³ Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Institute of Pathology, Charité, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁴ Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
⁶ Department of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
⁷ Department of Neurosurgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
⁸ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
⁹ Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
¹⁰ State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
¹¹ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Electronic address: taojiang1964@163.com.
¹² Department of Neurosurgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: chenzhp@sysucc.org.cn.
¹³ Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: rameen@broadinstitute.org.
¹⁴ Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA. Electronic address: jean_zhao@dfci.harvard.edu.
¹⁵ Department of Neurosurgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: mouyg@sysucc.org.cn.

Abstract

Glioblastoma multiforme (GBM) shows profound inter- and intratumoral heterogeneity, but differences across ancestries remain understudied. We assemble the largest cohort of GBMs from East Asian patients (EAS-GBM) and perform genomic and transcriptomic analyses. Transcriptomic clustering reveals distinct EAS-GBM molecular subtypes-proliferative (PL), neurosynaptic (NS), metabolic (MB), and immunomodulatory (IM)-based on activated biological pathways. We also identify protein markers enabling subtype classification in pathology. Comparative analysis with the predominantly European-ancestry The Cancer Genome Atlas (TCGA) GBM dataset (EUR-GBM) reveals similar main drivers, though EAS-GBMs lack the epidermal growth factor receptor (EGFR)-defined classical EUR-GBM subtype. EAS PL-GBMs display CCNE1/CCND2 overexpression, with myelocytomatosis viral oncogene (MYC) signaling activation. The IM-GBM cluster exhibits an immunotherapy-responsive expression profile, corroborated by improved overall survival under immune checkpoint blockade in an external dataset. Together, our data reveal distinctive genomic features of EAS-GBMs that may inform patient stratification for targeted therapy and drug development tailored to the EAS population.

Keywords: East Asian patients; genomic landscape; glioblastoma multiforme; immunological profile; molecular subtypes.

MeSH terms

Asia, Eastern
Brain Neoplasms* / genetics
Brain Neoplasms* / immunology
East Asian People / genetics
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genomics* / methods
Glioblastoma* / genetics
Glioblastoma* / immunology
Glioblastoma* / pathology
Humans
Male
Middle Aged
Transcriptome / genetics

Grants and funding

R01 CA262462/CA/NCI NIH HHS/United States