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Multi-omics analysis identifies osteosarcoma subtypes with distinct prognosis indicating stratified treatment.
Jiang, Yafei; Wang, Jinzeng; Sun, Mengxiong; Zuo, Dongqing; Wang, Hongsheng; Shen, Jiakang; Jiang, Wenyan; Mu, Haoran; Ma, Xiaojun; Yin, Fei; Lin, Jun; Wang, Chongren; Yu, Shuting; Jiang, Lu; Lv, Gang; Liu, Feng; Xue, Linghang; Tian, Kai; Wang, Gangyang; Zhou, Zifei; Lv, Yu; Wang, Zhuoying; Zhang, Tao; Xu, Jing; Yang, Liu; Zhao, Kewen; Sun, Wei; Tang, Yujie; Cai, Zhengdong; Wang, Shengyue; Hua, Yingqi.
Afiliação
  • Jiang Y; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Wang J; National Research Center for Translational Medicine (Shanghai), State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.
  • Sun M; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Zuo D; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Wang H; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Shen J; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Jiang W; Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, 200001, Shanghai, PR China.
  • Mu H; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Ma X; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Yin F; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Lin J; Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Wang C; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Yu S; National Research Center for Translational Medicine (Shanghai), State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.
  • Jiang L; National Research Center for Translational Medicine (Shanghai), State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.
  • Lv G; National Research Center for Translational Medicine (Shanghai), State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.
  • Liu F; National Research Center for Translational Medicine (Shanghai), State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.
  • Xue L; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Tian K; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Wang G; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Zhou Z; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Lv Y; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Wang Z; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Zhang T; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Xu J; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Yang L; National Research Center for Translational Medicine (Shanghai), State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.
  • Zhao K; Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, 200001, Shanghai, PR China.
  • Sun W; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
  • Tang Y; Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, 200001, Shanghai, PR China.
  • Cai Z; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China. caizhengdong@sjtu.edu.cn.
  • Wang S; National Research Center for Translational Medicine (Shanghai), State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China. wsy12115@rjh.com.cn.
  • Hua Y; Department of Orthopedic Oncology, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China. yhua@shsmu.edu.cn.
Nat Commun ; 13(1): 7207, 2022 11 23.
Article em En | MEDLINE | ID: mdl-36418292
Osteosarcoma (OS) is a primary malignant bone tumor that most commonly affects children, adolescents, and young adults. Here, we comprehensively analyze genomic, epigenomic and transcriptomic data from 121 OS patients. Somatic mutations are diverse within the cohort, and only TP53 is significantly mutated. Through unsupervised integrative clustering of the multi-omics data, we classify OS into four subtypes with distinct molecular features and clinical prognosis: (1) Immune activated (S-IA), (2) Immune suppressed (S-IS), (3) Homologous recombination deficiency dominant (S-HRD), and (4) MYC driven (S-MD). MYC amplification with HR proficiency tumors is identified with a high oxidative phosphorylation signature resulting in resistance to neoadjuvant chemotherapy. Potential therapeutic targets are identified for each subtype, including platinum-based chemotherapy, immune checkpoint inhibitors, anti-VEGFR, anti-MYC and PARPi-based synthetic lethal strategies. Our comprehensive integrated characterization provides a valuable resource that deepens our understanding of the disease, and may guide future clinical strategies for the precision treatment of OS.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ósseas / Osteossarcoma Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ósseas / Osteossarcoma Idioma: En Ano de publicação: 2022 Tipo de documento: Article