Genome-wide transcriptional sequencing identifies novel mutations in metabolic genes in human hepatocellular carcinoma

Daoud M. Meerzaman, Chunhua Yan, Qing Rong Chen, Michael N. Edmonson, Carl F. Schaefer, Robert J. Clifford, Barbara K. Dunn, L. I. Dong, Richard P. Finney, Constance M. Cultraro, Ying Hu, Zhihui Yang, C. U.V. Nguyen, Jenny M. Kelley, Shuang Cai, Hongen Zhang, Jinghui Zhang, Rebecca Wilson, Lauren Messmer, Young Hwa ChungJeong A. Kim, Neung Hwa Park, Myung Soo Lyu, I. L.Han Song, George Komatsoulis, Kenneth H. Buetow

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalCancer Genomics and Proteomics
Volume11
Issue number1
StatePublished - 2014

Keywords

  • Gene expression
  • Hepatocellular carcinoma (HCC)
  • Mutation
  • RNA-seq

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Meerzaman, D. M., Yan, C., Chen, Q. R., Edmonson, M. N., Schaefer, C. F., Clifford, R. J., Dunn, B. K., Dong, L. I., Finney, R. P., Cultraro, C. M., Hu, Y., Yang, Z., Nguyen, C. U. V., Kelley, J. M., Cai, S., Zhang, H., Zhang, J., Wilson, R., Messmer, L., ... Buetow, K. H. (2014). Genome-wide transcriptional sequencing identifies novel mutations in metabolic genes in human hepatocellular carcinoma. Cancer Genomics and Proteomics, 11(1), 1-12.