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 Buetow

Research output: Contribution to journalArticle

14 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Tumors
Hepatocellular Carcinoma
Genes
Genome
Mutation
Gene Expression
Neoplasms
Wnt Signaling Pathway
Metabolic Diseases
Medical problems
Electric network analysis
Transcriptome
Gene expression
Liver
Transcription Factors
Obesity
Datasets

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Cancer Research
  • Biochemistry
  • Medicine(all)

Cite this

Meerzaman, D. M., Yan, C., Chen, Q. R., Edmonson, M. N., Schaefer, C. F., Clifford, R. J., ... Buetow, K. (2014). Genome-wide transcriptional sequencing identifies novel mutations in metabolic genes in human hepatocellular carcinoma. Cancer Genomics and Proteomics, 11(1), 1-12.

Genome-wide transcriptional sequencing identifies novel mutations in metabolic genes in human hepatocellular carcinoma. / Meerzaman, Daoud M.; Yan, Chunhua; Chen, Qing Rong; Edmonson, Michael N.; Schaefer, Carl F.; Clifford, Robert J.; Dunn, Barbara K.; Dong, L. I.; Finney, Richard P.; Cultraro, Constance M.; Hu, Ying; Yang, Zhihui; Nguyen, C. U V; Kelley, Jenny M.; Cai, Shuang; Zhang, Hongen; Zhang, Jinghui; Wilson, Rebecca; Messmer, Lauren; Chung, Young Hwa; Kim, Jeong A.; Park, Neung Hwa; Lyu, Myung Soo; Song, I. L Han; Komatsoulis, George; Buetow, Kenneth.

In: Cancer Genomics and Proteomics, Vol. 11, No. 1, 2014, p. 1-12.

Research output: Contribution to journalArticle

Meerzaman, DM, Yan, C, Chen, QR, Edmonson, MN, Schaefer, CF, Clifford, RJ, Dunn, BK, Dong, LI, Finney, RP, Cultraro, CM, Hu, Y, Yang, Z, Nguyen, CUV, Kelley, JM, Cai, S, Zhang, H, Zhang, J, Wilson, R, Messmer, L, Chung, YH, Kim, JA, Park, NH, Lyu, MS, Song, ILH, Komatsoulis, G & Buetow, K 2014, 'Genome-wide transcriptional sequencing identifies novel mutations in metabolic genes in human hepatocellular carcinoma', Cancer Genomics and Proteomics, vol. 11, no. 1, pp. 1-12.
Meerzaman, Daoud M. ; Yan, Chunhua ; Chen, Qing Rong ; Edmonson, Michael N. ; Schaefer, Carl F. ; Clifford, Robert J. ; Dunn, Barbara K. ; Dong, L. I. ; Finney, Richard P. ; Cultraro, Constance M. ; Hu, Ying ; Yang, Zhihui ; Nguyen, C. U V ; Kelley, Jenny M. ; Cai, Shuang ; Zhang, Hongen ; Zhang, Jinghui ; Wilson, Rebecca ; Messmer, Lauren ; Chung, Young Hwa ; Kim, Jeong A. ; Park, Neung Hwa ; Lyu, Myung Soo ; Song, I. L Han ; Komatsoulis, George ; Buetow, Kenneth. / Genome-wide transcriptional sequencing identifies novel mutations in metabolic genes in human hepatocellular carcinoma. In: Cancer Genomics and Proteomics. 2014 ; Vol. 11, No. 1. pp. 1-12.
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AU - Messmer, Lauren

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AU - Kim, Jeong A.

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AU - Lyu, Myung Soo

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AU - Komatsoulis, George

AU - Buetow, Kenneth

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