Dataset Information

Relatively Small Contribution of Methylation and Genomic Copy Number Aberration to the Aberrant Expression of Inflammation-Related Genes in HBV-Related Hepatocellular Carcinoma.

ABSTRACT:

Background

It is well known that chronic inflammation plays a pivotal role in the development of hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). However, the causes behind aberrant expression of inflammation-related genes occurred in HCC remain unclear.

Methods

We performed array-based analyses to comprehensively investigate the contributions of DNA methylation and somatic copy number aberration (SCNA) to the aberrant expression of 1,027 inflammation-related genes in 30 HCCs and paired non-tumor tissues. The results were validated in public datasets and an additional sample set of 47 paired HCCs and non-tumor tissues.

Results

We identified 252 differentially expressed, 125 aberrantly methylated and 287 copy number changed inflammation-related genes. Despite reasonable statistical power, among them, only 11 genes and 56 genes whose aberrant expression was associated with DNA methylation or SCNA, respectively. DNA methylation and SCNA together contributed to less than 30% aberrant expression of inflammation-related genes.

Conclusion

These results suggest that molecular mechanisms other than DNA methylation and SCNA might play major role in the regulation of aberrant expression of inflammation-related gene in HBV-related HCCs.

SUBMITTER: Yu D

PROVIDER: S-EPMC4429029 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Relatively Small Contribution of Methylation and Genomic Copy Number Aberration to the Aberrant Expression of Inflammation-Related Genes in HBV-Related Hepatocellular Carcinoma.

Yu Dianke D Zhang Guosheng G Huang Xudong X Wu Chen C Tan Wen W Qiao Yan Y Chang Jiang J Zhao Hong H Bi Xinyu X Cai Jianqiang J Li Yun Y Lin Dongxin D

PloS one 20150512 5

<h4>Background</h4>It is well known that chronic inflammation plays a pivotal role in the development of hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). However, the causes behind aberrant expression of inflammation-related genes occurred in HCC remain unclear.<h4>Methods</h4>We performed array-based analyses to comprehensively investigate the contributions of DNA methylation and somatic copy number aberration (SCNA) to the aberrant expression of 1,027 inflammation-related genes ...[more]

PMID: 25965583

Similar Datasets

Project description:BackgroundGenomic DNA copy number aberrations are frequent in solid tumors, although the underlying causes of chromosomal instability in tumors remain obscure. Genes likely to have genomic instability phenotypes when mutated (e.g. those involved in mitosis, replication, repair, and telomeres) are rarely mutated in chromosomally unstable sporadic tumors, even though such mutations are associated with some heritable cancer prone syndromes.MethodsWe applied array comparative genomic hybridization (CGH) to the analysis of breast tumors. The variation in the levels of genomic instability amongst tumors prompted us to investigate whether alterations in processes/genes involved in maintenance and/or manipulation of the genome were associated with particular types of genomic instability.ResultsWe discriminated three breast tumor subtypes based on genomic DNA copy number alterations. The subtypes varied with respect to level of genomic instability. We find that shorter telomeres and altered telomere related gene expression are associated with amplification, implicating telomere attrition as a promoter of this type of aberration in breast cancer. On the other hand, the numbers of chromosomal alterations, particularly low level changes, are associated with altered expression of genes in other functional classes (mitosis, cell cycle, DNA replication and repair). Further, although loss of function instability phenotypes have been demonstrated for many of the genes in model systems, we observed enhanced expression of most genes in tumors, indicating that over expression, rather than deficiency underlies instability.ConclusionMany of the genes associated with higher frequency of copy number aberrations are direct targets of E2F, supporting the hypothesis that deregulation of the Rb pathway is a major contributor to chromosomal instability in breast tumors. These observations are consistent with failure to find mutations in sporadic tumors in genes that have roles in maintenance or manipulation of the genome.

Dataset Information

Relatively Small Contribution of Methylation and Genomic Copy Number Aberration to the Aberrant Expression of Inflammation-Related Genes in HBV-Related Hepatocellular Carcinoma.

Background

Methods

Results

Conclusion

Publications

Relatively Small Contribution of Methylation and Genomic Copy Number Aberration to the Aberrant Expression of Inflammation-Related Genes in HBV-Related Hepatocellular Carcinoma.

Similar Datasets

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