RT Journal Article
SR Electronic
T1 Single-cell and single-variant resolution analysis of clonal evolution in human liver cancer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.30.424907
DO 10.1101/2020.12.30.424907
A1 Xianbin Su
A1 Linan Zhao
A1 Yi Shi
A1 Rui Zhang
A1 Qi Long
A1 Shihao Bai
A1 Qing Luo
A1 Yingxin Lin
A1 Xin Zou
A1 Shila Ghazanfar
A1 Kun Tao
A1 Guoliang Yang
A1 Lan Wang
A1 Kun-Yan He
A1 Xiaofang Cui
A1 Jian He
A1 Jiao-Xiang Wu
A1 Bo Han
A1 Na Wang
A1 Xiaolin Li
A1 Pengyi Yang
A1 Shangwei Hou
A1 Jielin Sun
A1 Jean Y. H. Yang
A1 Jinhong Chen
A1 Ze-Guang Han
YR 2021
UL http://biorxiv.org/content/early/2021/01/02/2020.12.30.424907.abstract
AB Genetic heterogeneity of tumor is closely related to clonal evolution, phenotypic diversity and treatment resistance. Such heterogeneity has been characterized in liver cancer at single-cell sub-chromosomal scale, and a more precise single-variant resolution analysis is lacking. Here we employed a strategy to analyze both the single-cell genomic mutations and transcriptomic changes in 5 patients with liver cancer. Target sequencing was done for a total of 480 single cells in a patient-specific manner. DNA copy number status of point mutations was obtained from single-cell mutational profiling. The clonal structures of liver cancers were then uncovered at single-variant resolution, and mutation combinations in single cells enabled reconstruction of their evolutionary history. A common origin but independent evolutionary fate was revealed for primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. The mutational signature suggested early evolutionary process may be related to specific etiology like aristolochic acids. By parallel single-cell RNA-Seq, the transcriptomic phenotype was found to be related with genetic heterogeneity in liver cancer. We reconstructed the single-cell and single-variant resolution clonal evolutionary history of liver cancer, and dissection of both genetic and phenotypic heterogeneity provides knowledge for mechanistic understanding of liver cancer initiation and progression.Competing Interest StatementThe authors have declared no competing interest.ADOallelic drop-outCNVcopy number variationHCChepatocellular carcinomaINDELinsertion or deletionPVTTportal vein tumor thrombusscRNA-Seqsingle-cell RNA-SeqSNVsingle-nucleotide variationVAFvariant allele frequencyWESwhole exome sequencingWGAwhole genome amplification.