title: Genome-wide transcriptional sequencing identifies novel mutations in metabolic genes in human hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Center for Biomedical Informatics & Information Technology, 9609 Medical Center Drive, 1W466, Rockville, MD 20850, U.S.A. meerzamd@mail.nih.gov.
authors.forename: Daoud M
authors.initials: DM
authors.lastname: Meerzaman
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yan
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Chen
authors.forename: Michael N
authors.initials: MN
authors.lastname: Edmonson
authors.forename: Carl F
authors.initials: CF
authors.lastname: Schaefer
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Clifford
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Dunn
authors.forename: Li
authors.initials: L
authors.lastname: Dong
authors.forename: Richard P
authors.initials: RP
authors.lastname: Finney
authors.forename: Constance M
authors.initials: CM
authors.lastname: Cultraro
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Yang
authors.forename: Cu V
authors.initials: CV
authors.lastname: Nguyen
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Kelley
authors.forename: Shuang
authors.initials: S
authors.lastname: Cai
authors.forename: Hongen
authors.initials: H
authors.lastname: Zhang
authors.forename: Jinghui
authors.initials: J
authors.lastname: Zhang
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wilson
authors.forename: Lauren
authors.initials: L
authors.lastname: Messmer
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
authors.forename: Jeong A
authors.initials: JA
authors.lastname: Kim
authors.forename: Neung Hwa
authors.initials: NH
authors.lastname: Park
authors.forename: Myung-Soo
authors.initials: MS
authors.lastname: Lyu
authors.forename: Il Han
authors.initials: IH
authors.lastname: Song
authors.forename: George
authors.initials: G
authors.lastname: Komatsoulis
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Buetow
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D015870:Gene Expression; D055106:Genome-Wide Association Study; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D012334:RNA, Neoplasm / Q000235:genetics; D059467:Transcriptome
chemical_list: D004273:DNA, Neoplasm; D012334:RNA, Neoplasm
keywords: Hepatocellular carcinoma (HCC); RNA-seq; gene expression; mutation