Oncotarget. 2017 Feb 17. doi: 10.18632/oncotarget.15428. [Epub ahead of print]
Whole genome sequencing of matched tumor, adjacent non-tumor tissues and corresponding normal blood samples of hepatocellular carcinoma patients revealed dynamic changes of the mutations profiles during hepatocarcinogenesis.
Mao R1,2, Liu J2, Liu G2, Jin S2, Xue Q3, Ma L2, Fu Y4, Zhao N2, Xing J5, Li L1, Qiu Y6, Lin B1,2,7.
Author information
1 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
2 Systems Biology Division, Zhejiang-California International Nanosystems Institute (ZCNI), Zhejiang University, Hangzhou, Zhejiang Province, P.R. China.
3 Departmant of Agronomy, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, P. R. China.
4 College of Animal Sciences, Zhejiang University, Hangzhou, P. R. China.
5 State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, China.
6 The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
7 Departmant of Urology, University of Washington, Seattle, USA.
Abstract
Hepatocellular carcinoma (HCC) has become the third most deadly disease worldwide and HBV is the major factor in Asia and Africa. We conducted 9 WGS (whole genome sequencing) analyses for matched samples of tumor, adjacent non-tumor tissues and normal blood samples of HCC patients from three HBV positive patients. We then validated the mutations identified in a larger cohort of 177 HCC patients. We found that the number of the unique somatic mutations (average of 59,136) in tumor samples is significantly less than that in adjacent non-tumor tissues (average 83, 633). We discovered that the TP53 R249S mutation occurred in 7.7% of the HCC patients, and it was significantly associated with poor diagnosis. In addition, we found that the L104P mutation in the VCX gene (Variable charge, X-linked) was absent in white blood cell samples, but present at 11.1% frequency in the adjacent tissues and increased to 14.6% in HCC tissues, suggesting that this mutation might be a tumor driver gene driving HCC carcinogenesis. Finally, we identified a TK1-RNU7 fusion, which would result in a deletion of 103 amino acids from its C-terminal. The frequencies of this fusion event decreased from the adjacent tissues (29.2%) to the tumors (16.7%), suggesting that a truncated thymidine Kinase1 (TK1) caused by the fusion event might be deleterious and be selected against during tumor progression. The three-way comparisons allow the identification of potential driver mutations of carcinogenesis. Furthermore, our dataset provides the research community a valuable dataset for identifying dynamic changes of mutation profiles and driver mutations for HCC.
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Oncotarget。 2017年2月17日。doi:10.18632 / oncotarget.15428。 [提前印刷]
肝细胞癌患者的匹配肿瘤,相邻非肿瘤组织和相应的正常血液样本的全基因组测序揭示了肝癌发生过程中突变特征的动态变化。
毛ao ao ao ao Liu Liu Liu Liu Liu Liu X X X X X X X X X Zhao Zhao Zhao X X X X X X X X Lin Lin Lin Lin Lin Lin Lin Lin Lin Lin。。
作者信息
Oncotarget。 2017年2月17日。doi:10.18632 / oncotarget.15428。 [提前印刷]
肝细胞癌患者的匹配肿瘤,相邻非肿瘤组织和相应的正常血液样本的全基因组测序揭示了肝癌发生过程中突变特征的动态变化。
毛ao ao ao ao Liu Liu Liu Liu Liu Liu X X X X X X X X X Zhao Zhao Zhao X X X X X X X X Lin Lin Lin Lin Lin Lin Lin Lin Lin Lin。。
作者信息