Genome-wide Transcriptional Sequencing Identifies Novel Mutations in Metabolic Genes in Human Hepatocellular Carcinoma

Cancer Genomics - Proteomics

JENNY M. KELLEY³  LAUREN MESSMER³  LI DONG³  ROBERT J. CLIFFORD³  YING HU⁶  JEONG A. KIM⁷  RICHARD P. FINNEY⁶  GEORGE KOMATSOULIS⁶  BARBARA K. DUNN⁴  CONSTANCE M. CULTRARO³  MICHAEL N. EDMONSON⁶  CU V. NGUYEN⁶  NEUNG HWA PARK⁵  CARL F. SCHAEFER⁶  IL HAN SONG²  QING-RONG CHEN⁶  KENNETH H. BUETOW⁸  REBECCA WILSON³  ZHIHUI YANG³  MYUNG-SOO LYU⁵  HONGEN ZHANG³  CHUNHUA YAN⁶  SHUANG CAI³  DAOUD M. MEERZAMAN⁸  YOUNG-HWA CHUNG⁷  JINGHUI ZHANG¹ 

[1] Center for Bioinformatics and Information Technology, National Cancer Institute, Rockville, MD, U.S.A. Department of Biotechnology/Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, U.S.A. Center for Bioinformatics and Information Technology, National Cancer Institute, Rockville, MD, U.S.A. Center for Bioinformatics and Information Technology, National Cancer Institute, Rockville, MD, U.S.A. Department of Biotechnology/Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, U.S.A. Department of Biotechnology/Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, U.S.A. Center for Bioinformatics and Information Technology, National Cancer Institute, Rockville, MD, U.S.A. Department of Biotechnology/Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, U.S.A.;Department of Internal Medicine, College of Medicine, Dankook University, Cheon-An, Korea Department of Internal Medicine, College of Medicine, Dankook University, Cheon-An, Korea Department of Internal Medicine, College of Medicine, Dankook University, Cheon-An, Korea;Laboratory of Population Genetics, National Cancer Institute, National Cancer Institute, Bethesda, MD, U.S.A. Laboratory of Population Genetics, National Cancer Institute, National Cancer Institute, Bethesda, MD, U.S.A. Laboratory of Population Genetics, National Cancer Institute, National Cancer Institute, Bethesda, MD, U.S.A.;Basic Prevention Science Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, U.S.A Basic Prevention Science Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, U.S.A Basic Prevention Science Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, U.S.A;Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea;Center for Bioinformatics and Information Technology, National Cancer Institute, Rockville, MD, U.S.A. Center for Bioinformatics and Information Technology, National Cancer Institute, Rockville, MD, U.S.A. Center for Bioinformatics and Information Technology, National Cancer Institute, Rockville, MD, U.S.A.;Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea;Center for Bioinformatics and Information Technology, National Cancer Institute, Rockville, MD, U.S.A. Laboratory of Population Genetics, National Cancer Institute, National Cancer Institute, Bethesda, MD, U.S.A. Center for Bioinformatics and Information Technology, National Cancer Institute, Rockville, MD, U.S.A. Center for Bioinformatics and Information Technology, National Cancer Institute, Rockville, MD, U.S.A. Laboratory of Population Genetics, National Cancer Institute, National Cancer Institute, Bethesda, MD, U.S.A. Laboratory of Population Genetics, National Cancer Institute, National Cancer Institute, Bethesda, MD, U.S.A. Center for Bioinformatics and Information Technology, National Cancer Institute, Rockville, MD, U.S.A. Laboratory of Population Genetics, National Cancer Institute, National Cancer Institute, Bethesda, MD, U.S.A.

关键词: Hepatocellular carcinoma (HCC);    RNA-seq;    gene expression;    mutation;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

We report on next-generation transcriptome sequencing results of three human hepatocellular carcinoma tumor/tumor-adjacent pairs. This analysis robustly examined ∼12,000 genes for both expression differences and molecular alterations. We observed 4,513 and 1,182 genes demonstrating 2-fold or greater increase or decrease in expression relative to their normal, respectively. Network analysis of expression data identified the Aurora B signaling, FOXM1 transcription factor network and Wnt signaling pathways pairs being altered in HCC. We validated as differential gene expression findings in a large data set containing of 434 liver normal/tumor sample pairs. In addition to known driver mutations in TP53 and CTNNB1, our mutation analysis identified non-synonymous mutations in genes implicated in metabolic diseases, i.e. diabetes and obesity: IRS1, HMGCS1, ATP8B1, PRMT6 and CLU, suggesting a common molecular etiology for HCC of alternative pathogenic origin.

【 授权许可】

Unknown