Whole-exome mutational landscape of metastasis in patient-derived hepatocellular carcinoma cells  

作　　者：Qian Zhou Zuli Li Linlan Song Di Mu Jin Wang Li Tian Yong Liao 

机构地区：[1]Key Laboratory of Molecular Biology on Infectious Diseases,Ministry of Education,Chongqing,China [2]Institute for Viral Hepatitis,Chongqing Medical University,Chongqing,China [3]Department of Infectious Diseases,Second Affiliated Hospital,Chongqing Medical University,Chongqing,China

出　　处：《Genes & Diseases》2020年第3期380-391,共12页基因与疾病（英文）

基　　金：This work was supported by the National Natural Science Foundation of China(NSFC,NO.81172066,NO.81472858;NO.91529103);Innovation Team Fund of Second Affiliated Hospital of Chongqing Medical University;The authors would like to thank Dr.Zhou-You Tang,Professor&Director,Liver Cancer Institute,Fudan University,for providing the three HCC cell lines(MHCC97-L,MHCC97-H,HCC97LM3).

摘　　要：In order to explore the genomic basis for liver cancer metastasis,whole-exome sequencing(WES)was performed on patient-derived hepatocellular carcinoma(HCC)cell lines with differential metastatic potentials and analyzed their clonal evolution relationships.An evolutionary tree based on genomic single nucleotide polymorphism(SNP)was constructed in MegaX software.The WES data showed that the average percentage of heterogeneous mutations in each HCC cell lines was 16.55%(range,15.38%e18.17%).C:G>T:A and T:A>C:G somatic transitions were the two most frequent substitutions.In these metastatic HCC cell lines,non-silent gene mutations were found in 21.88%of known driver genes and 10 classical signaling pathways.The protein interaction network was constructed by STRING,and hub genes were found in the shared trunk mutation genes and the heterogeneous branch mutations respectively.In cBioPortal database,some of the selected hub genes were found to be associated with poor overall survival(OS)of HCC patients.Among the mutated HCC driver genes,a novel KEAP1 mutation with a homozygous frameshift truncation at the c-terminal Nrf2 binding region was detected and verified in MHCC97-H and HCC97LM3 cells.In conclusion,WES data demonstrate that HCC cell lines from tumor biopsy specimens of the same patient have obtained different metastatic potentials through repeated selection in rodents in vivo,and they do indeed have a genetic relationship at the genomic level.

关 键 词：Clonal evolution Encyclopedia of genes and genomes(KEGG) Gene ontology(GO) Genome-wide association Hepatocellular carcinoma Metastatic potentiality Somatic gene mutation Whole exome sequencing 

分 类 号：R735.7[医药卫生—肿瘤]