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 Chung; Jeong A. Kim; Neung Hwa Park; Myung Soo Lyu; I. L.Han Song; George Komatsoulis; Kenneth H. Buetow

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 journal › Article › peer-review

20 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 language	English (US)
Pages (from-to)	1-12
Number of pages	12
Journal	Cancer Genomics and Proteomics
Volume	11
Issue number	1
State	Published - 2014
Externally published	Yes

Keywords

Gene expression
Hepatocellular carcinoma (HCC)
Mutation
RNA-seq

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics
Cancer Research

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.

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, KH 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.

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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.",

keywords = "Gene expression, Hepatocellular carcinoma (HCC), Mutation, RNA-seq",

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

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AU - Meerzaman, Daoud M.

AU - Yan, Chunhua

AU - Chen, Qing Rong

AU - Edmonson, Michael N.

AU - Schaefer, Carl F.

AU - Clifford, Robert J.

AU - Dunn, Barbara K.

AU - Dong, L. I.

AU - Finney, Richard P.

AU - Cultraro, Constance M.

AU - Hu, Ying

AU - Yang, Zhihui

AU - Nguyen, C. U.V.

AU - Kelley, Jenny M.

AU - Cai, Shuang

AU - Zhang, Hongen

AU - Zhang, Jinghui

AU - Wilson, Rebecca

AU - Messmer, Lauren

AU - Chung, Young Hwa

AU - Kim, Jeong A.

AU - Park, Neung Hwa

AU - Lyu, Myung Soo

AU - Song, I. L.Han

AU - Komatsoulis, George

AU - Buetow, Kenneth H.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Gene expression

KW - Hepatocellular carcinoma (HCC)

KW - Mutation

KW - RNA-seq

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

Abstract

Keywords

ASJC Scopus subject areas

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