Genomic sequencing identifies a few mutations driving the independent origin of primary liver tumors in a chronic hepatitis murine model

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	Genomic sequencing identifies a few mutations driving the independent origin of primary liver tumors in a chronic hepatitis murine model
	Yang, ZY; Jia, MM; Liu, GJ; Hao, HN; Chen, L; Li, GH; Liu, SX; Li, YW; Wu, CI; Lu, XM; Wang, SD
	2017
发表期刊	PLOS ONE
ISSN	1932-6203
卷号	12 期号:11
摘要	With the development of high-throughput genomic analysis, sequencing a mouse primary cancer model provides a new opportunity to understand fundamental mechanisms of tumorigenesis and progression. Here, we characterized the genomic variations in a hepatitis related primary hepatocellular carcinoma (HCC) mouse model. A total of 12 tumor sections and four adjacent non-tumor tissues from four mice were used for whole exome and/or whole genome sequencing and validation of genotyping. The functions of the mutated genes in tumorigenesis were studied by analyzing their mutation frequency and expression in clinical HCC samples. A total of 46 single nucleotide variations (SNVs) were detected within coding regions. All SNVs were only validated in the sequencing samples, except the Hras mutation, which was shared by three tumors in the M1 mouse. However, the mutated allele frequency varied from high (0.4) to low (0.1), and low frequency (0.1-0.2) mutations existed in almost every tumor. Together with a diploid karyotype and an equal distribution pattern of these SNVs within the tumor, these results suggest the existence of subclones within tumors. A total of 26 mutated genes were mapped to 17 terms describing different molecular and cellular functions. All 41 human homologs of the mutated genes were mutated in the clinical samples, and some mutations were associated with clinical outcomes, suggesting a high probability of cancer driver genes in the spontaneous tumors of the mouse model. Genomic sequencing shows that a few mutations can drive the independent origin of primary liver tumors and reveals high heterogeneity among tumors in the early stage of hepatitis-related primary hepatocellular carcinoma.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13651
专题	个人在本单位外知识产出
推荐引用方式 GB/T 7714	Yang, ZY,Jia, MM,Liu, GJ,et al. Genomic sequencing identifies a few mutations driving the independent origin of primary liver tumors in a chronic hepatitis murine model[J]. PLOS ONE,2017,12(11).
APA	Yang, ZY.,Jia, MM.,Liu, GJ.,Hao, HN.,Chen, L.,...&Wang, SD.(2017).Genomic sequencing identifies a few mutations driving the independent origin of primary liver tumors in a chronic hepatitis murine model.PLOS ONE,12(11).
MLA	Yang, ZY,et al."Genomic sequencing identifies a few mutations driving the independent origin of primary liver tumors in a chronic hepatitis murine model".PLOS ONE 12.11(2017).

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