| Description |
As the development of high-throughput genomic analysis, sequencing mouse primary cancer model provides a new opportunity to understand fundamental mechanisms of tumorigenesis and progression. Here, we sought to characterize the genomic variations in a hepatitis-related primary hepatocellular carcinoma (HCC) mouse model.12 tumor sections and adjacent non-tumor tissues from four mice were used for WES and/or WGS and validation of genotyping. The functions of the mutated genes in tumorigenesis were studied by analysis of their mutation frequency and expression in clinical HCC samples. Total 46 single nucleotide variations (SNVs) at coding regions were detected. All the SNVs were only validated in the sequencing samples, except Hras mutation shared by three tumors in M1 mouse. The mutated allele frequency varies from high (0.4) to low (0.1), and low frequency (0.1~0.2) mutations exist in almost every tumor. Together with diploid karyotype, relatively high purity of hepatitis cells, equally distribution pattern of these SNVs within tumor, these results suggest the existence of subclones within tumors. In addition, 26 mutated genes were mapped to 17 terms describing different molecular and cellular functions, and all 41 human homologous were mutated in clinical samples and 37 genes were associated with cancer specific biological processes, implying the high probability of cancer driver genes in the spontaneous tumors of mouse model. Genomic sequencing identifies a few mutations can drive independent origin of primary liver tumors and reveals great heterogeneity among tumors in the chronic hepatitis murine model.
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