Whole-exome sequencing identifies mutated PCK2 and HUWE1 associated with carcinoma cell proliferation in a hepatocellular carcinoma patient

Liu,Yan-Xuan; Zhang,Shu-Fang; Ji,Ying-Hua; Guo,Sheng‑Ju; Wang,Geng-Fu; Zhang,Guang-Wen

doi:10.3892/ol.2012.825

Whole-exome sequencing identifies mutated PCK2 and HUWE1 associated with carcinoma cell proliferation in a hepatocellular carcinoma patient

Authors:
- Yan-Xuan Liu
- Shu-Fang Zhang
- Ying-Hua Ji
- Sheng‑Ju Guo
- Geng-Fu Wang
- Guang-Wen Zhang
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Affiliations: Department of Genetic Disease, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, P.R. China, Central Laboratory, Affiliated Haikou Hospital Xiangya School of Medicine Central South University (Haikou Municipal People's Hospital), Haikou, Hainan 570208, P.R. China, Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, P.R. China, Department of Pharmaceutics, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, P.R. China, Department of Anesthesiology, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, P.R. China, Department of Infectious Diseases, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, P.R. China
Published online on: July 26, 2012 https://doi.org/10.3892/ol.2012.825
Pages: 847-851

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Abstract

Hepatocellular carcinoma (HCC) is diagnosed in more than half a million individuals worldwide every year. It is often invasive and metastatic, resulting in a poor prognosis. Our knowledge of the genomic alterations implicated in HCC initiation and progression is fragmentary, and few molecular alterations unique to HCC are known. We performed whole‑exome sequencing for a pleomorphic cell‑type HCC tissue and matched normal tissue, and uncovered seven non‑synonymous somatic variants in SPATA21, PPCS, CDH12, OR1L3, PCK2, HUWE1 and PHF16. These variants were validated by PCR and sequencing, with the exception of that in PPCS. We further performed a bioinformatics analysis of the six validated variants. The results suggested that the function of the proteins of the three mutated genes, PCK2, HUWE1 and PHF16, may be changed significantly. Among these genes, PCK2, within the insulin signaling pathway, and HUWE1, within the ubiquitin-mediated proteolysis pathway, may be essential for cell proliferation. These pathways are known to be important for hepatocarcinogenesis. Hence, we suggest that PCK2 and HUWE1 are associated with carcinoma cell proliferation in HCC.

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