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

October 2012 Volume 4 Issue 4

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

October 2012 Volume 4 Issue 4

Full Size Image

Article

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
View Affiliations / Copyright

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
Pages: 847-851
|
Published online on: July 26, 2012

https://doi.org/10.3892/ol.2012.825
Expand metrics +

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.

View Figures

View References

1.	D Motola-KubaD Zamora-ValdésM UribeN Méndez- SánchezHepatocellular carcinoma. An overviewAnn Hepatol516242006
2.	P SrivatanakulH SriplungS DeerasameeEpidemiology of liver cancer: an overviewAsian Pac J Cancer Prev51181252004
3.	KA McGlynnWT LondonEpidemiology and natural history of hepatocellular carcinomaBest Pract Res Clin Gastroenterol19323200510.1016/j.bpg.2004.10.00415757802
4.	JM ClarkThe epidemiology of nonalcoholic fatty liver disease in adultsJ Clin Gastroenterol40Suppl 1S5S10200616540768
5.	EK TeoKM FockHepatocellular carcinoma: an Asian perspectiveDig Dis19263268200110.1159/00005069211935085
6.	H LiR DurbinFast and accurate long-read alignment with Burrows-Wheeler transformBioinformatics26589595201010.1093/bioinformatics/btp69820080505
7.	H LiB HandsakerA Wysoker1000 Genome Project Data Processing Subgroup: The Sequence Alignment/Map format and SAMtoolsBioinformatics2520782079200910.1093/bioinformatics/btp35219505943
8.	DC KoboldtQ ZhangDE LarsonVarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencingGenome Res22568576201210.1101/gr.129684.11122300766
9.	JT RobinsonH ThorvaldsdóttirW WincklerIntegrative genomics viewerNat Biotechnol292426201110.1038/nbt.1754
10.	KS PollardMJ HubiszKR RosenbloomA SiepelDetection of nonneutral substitution rates on mammalian phylogeniesGenome Res20110121201010.1101/gr.097857.10919858363
11.	JM SchwarzC RödelspergerM SchuelkeD SeelowMutationTaster evaluates disease-causing potential of sequence alterationsNat Methods7575576201010.1038/nmeth0810-57520676075
12.	C ColeJD BarberGJ BartonThe Jpred 3 secondary structure prediction serverNucleic Acids Res36W197W201200810.1093/nar/gkn23818463136
13.	JM LlovetAM Di BisceglieJ BruixPanel of Experts in HCC-Design Clinical Trials: Design and endpoints of clinical trials in hepatocellular carcinomaJ Natl Cancer Inst100698711200810.1093/jnci/djn134
14.	Y EdamotoA HaraW BiernatAlterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosisInt J Cancer106334341200310.1002/ijc.11254
15.	P HainautM Hollsteinp53 and human cancer: the first ten thousand mutationsAdv Cancer Res7781137200010.1016/S0065-230X(08)60785-X10549356
16.	M PollakInsulin and insulin-like growth factor signalling in neoplasiaNat Rev Cancer8915928200810.1038/nrc253619029956
17.	D SachdevD YeeDisrupting insulin-like growth factor signaling as a potential cancer therapyMol Cancer Ther6112200710.1158/1535-7163.MCT-06-008017237261
18.	P Laurent-PuigJ Zucman-RossiGenetics of hepatocellular tumorsOncogene2537783786200610.1038/sj.onc.1209547
19.	SH TangDH YangW HuangHK ZhouXH LuG YeHypomethylated P4 promoter induces expression of the insulin-like growth factor-II gene in hepatocellular carcinoma in a Chinese populationClin Cancer Res1241714177200610.1158/1078-0432.CCR-05-226116857788
20.	AT De SouzaGR HankinsMK WashingtonTC OrtonRL JirtleM6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosityNat Genet1144744919957493029
21.	T HanafusaY YumotoK NousoReduced expression of insulin-like growth factor binding protein-3 and its promoter hypermethylation in human hepatocellular carcinomaCancer Lett176149158200210.1016/S0304-3835(01)00736-4
22.	V TovarC AlsinetA VillanuevaIGF activation in a molecular subclass of hepatocellular carcinoma and pre-clinical efficacy of IGF-1R blockageJ Hepatol52550559201010.1016/j.jhep.2010.01.01520206398
23.	SO KimJG ParkYI LeeIncreased expression of the insulin-like growth factor I (IGF-I) receptor gene in hepatocellular carcinoma cell lines: implications of IGF-I receptor gene activation by hepatitis B virus X gene productCancer Res563831383619968706031
24.	MR HillRE McCallumIdentification of tumor necrosis factor as a transcriptional regulator of the phosphoenolpyruvate carboxykinase gene following endotoxin treatment of miceInfect Immun60404040501992
25.	A VillanuevaP NewellDY ChiangSL FriedmanJM LlovetGenomics and signaling pathways in hepatocellular carcinomaSemin Liver Dis275576200710.1055/s-2006-96017117295177

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

This article is mentioned in:

Abstract

Figure 1

Related Articles