Clonal evolution in liver cancer at single-cell and single-variant resolution
Xianbin Su, Linan Zhao, Yi Shi, Rui Zhang, Qi Long, Shihao Bai, Qing Luo, Yingxin Lin, Xin Zou, Shila Ghazanfar, Kun Tao, Guoliang Yang, Lan Wang, Kun-Yan He, Xiaofang Cui, Jian He, Jiao-Xiang Wu, Bo Han, Bin Yan, Biao Deng, Na Wang, Xiaolin Li, Pengyi Yang, Shangwei Hou, Jielin Sun, Jean Yang, Jinhong Chen, Ze‐Guang Han
Abstract
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.