Clonal evolution in liver cancer at single-cell and single-variant resolution

Journal of Hematology & Oncology

Yi Shi¹  Shila Ghazanfar²  Rui Zhang³  Jinhong Chen³  Bin Yan⁴  Biao Deng⁴  Kun Tao⁵  Guoliang Yang⁶  Jiao-Xiang Wu⁷  Shangwei Hou⁷  Bo Han⁷  Qi Long⁸  Xiaofang Cui⁹  Na Wang⁹  Jian He⁹  Xin Zou⁹  Kun-Yan He⁹  Linan Zhao⁹  Ze-Guang Han⁹  Jielin Sun⁹  Xiaolin Li⁹  Lan Wang⁹  Xianbin Su⁹  Qing Luo⁹  Shihao Bai⁹  Yingxin Lin^1,10  Jean Y. H. Yang^1,10  Pengyi Yang^1,11 

[1] Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai, China;Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, CB2 0RE, Cambridge, UK;Department of General Surgery, Huashan Hospital and Cancer Metastasis Institute, Fudan University, Shanghai, China;Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Pathology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Key Laboratory for Regenerative Medicine (Ministry of Education), School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China;Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China;School of Mathematics and Statistics and Charles Perkins Center, The University of Sydney, Sydney, Australia;School of Mathematics and Statistics and Charles Perkins Center, The University of Sydney, Sydney, Australia;Computational Systems Biology Group, Children’s Medical Research Institute, The University of Sydney, 2145, Westmead, NSW, Australia;

关键词: Hepatocellular carcinoma;    Genetic heterogeneity;    Somatic mutation;    Clonal structure;    Tumor evolution;   

DOI  :  10.1186/s13045-021-01036-y

来源: Springer

【 摘 要 】

Genetic heterogeneity of tumor is closely related to its clonal evolution, phenotypic diversity and treatment resistance, and such heterogeneity has only been characterized at single-cell sub-chromosomal scale in liver cancer. Here we reconstructed the single-variant resolution clonal evolution in human liver cancer based on single-cell mutational profiles. The results indicated that key genetic events occurred early during tumorigenesis, and an early metastasis followed by independent evolution was observed in primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. By parallel single-cell RNA-Seq, the transcriptomic phenotype of HCC was found to be related with genetic heterogeneity. For the first time we reconstructed the single-cell and single-variant clonal evolution in human liver cancer, and dissection of both genetic and phenotypic heterogeneity will facilitate better understanding of their relationship.

【 授权许可】

CC BY