Genome-wide integrative analysis revealed a correlation between lengths of copy number segments and corresponding gene expression profile.

Ken Miyaguch,Hiroyuki Uetake,Toshiaki Ishikawa,Mahmut Yasen,Kenichi Sugihara,Hiroshi Mizushima,Hiroshi Tanaka,Shigeki Arii,Shota Nemoto,Yutaka Fukuoka,Shinji Tanaka

doi:10.6026/97320630007280

Ken Miyaguch, Hiroyuki Uetake + Show 9 more

Open Access

https://doi.org/10.6026/97320630007280

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Journal: Bioinformation	Publication Date: Nov 20, 2011
Citations: 4	License type: cc-by

Affiliation: Tokyo Medical and Dental University

Abstract

Microarray analysis has been applied to comprehensively reveal the abnormalities of DNA copy number (CN) and gene expression in human cancer research during the last decade. These analyses have individually contributed to identify the genes associated with carcinogenesis, progression, metastasis of tumor cells and poor prognosis of cancer patients. However, it is known that the correlation between profiles of CN and gene expression does not highly correlate. Factors which determine the degree of correlation remain largely unexplained. To investigate one such factor, we performed trend analyses between the lengths of CN segments and corresponding gene expression profiles from microarray data in hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC). Significant correlations were observed in CN gain of HCC and CRC (p<0.05). The trend of the CN loss showed a significant correlation in HCC although there was no correlation between the length of CN loss segments and gene expression in CRC. Our findings suggest that the influence of CN on gene expression highly depends on the length of CN region, especially in the case of CN gain. To the best of our knowledge, this is the first study describing the correlation between lengths of CNA segments and expression profiles of corresponding genes.

Highlights

In late years, relations of carcinogenesis and copy number alteration (CNA) attract attention in conjunction with impaired expression of genes
Comprehensive analyses for either genomic CNAs or gene expressions have been frequently performed by a number of researchers, the precedence study has rarely reported in genome-wide correlation between CNAs and abnormal gene expressions [6, 7, 8, 9]
We hypothesized that the expressions of genes encoded on a long CNA segment tend to be more susceptible for copy number changes than genes on a shorter CNA segment because a wide range of chromosomal region covers more valuable sequences for genes to be efficiently translated from genomic DNA. Those gene expressions may show changes positively correlated with patterns of altered copy numbers; down-regulation for loss/deletion, up-regulation for gain/amplification. This is the first report discussing about the association between genomic lengths of genome-wide CNAs and expressions of genes encoded on those CNA segments by analyzing the data from microarrays for human hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC)

Summary

Introduction

Relations of carcinogenesis and copy number alteration (CNA) attract attention in conjunction with impaired expression of genes. In addition to CNA profiles such as loss/deletion and gain/amplification, the length of the genomic mutation is possibly another factor to cause expression changes of genes encoded on the genomic region which has an abnormality in DNA copy number. We hypothesized that the expressions of genes encoded on a long CNA segment tend to be more susceptible for copy number changes than genes on a shorter CNA segment because a wide range of chromosomal region covers more valuable sequences for genes to be efficiently translated from genomic DNA.

Results

Conclusion