Exploring breast carcinogenesis through integrative genomics and epigenomics analyses

Chin Mining, Norfilza Mohd Mokhtar, Norlia Abdullah, Rohaizak Muhammad, Nor Aina Emran, Siti Aishah Md Ali, Roslan Harun, A. Rahman A. Jamal

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

There have been many DNA methylation studies on breast cancer which showed various methylation patterns involving tumour suppressor genes and oncogenes but only a few of those studies link the methylation data with gene expression. More data are required especially from the Asian region and to analyse how the epigenome data correlate with the transcriptome. DNA methylation profiling was carried out on 76 fresh frozen primary breast tumour tissues and 25 adjacent non-cancerous breast tissues using the Illumina Infinium® HumanMethylation27 BeadChip. Validation of methylation results was performed on 7 genes using either MS-MLPA or MS-qPCR. Gene expression profiling was done on 15 breast tumours and 5 adjacent non-cancerous breast tissues using the Affymetrix GeneChip® Human Gene 1.0 ST array. The overlapping genes between DNA methylation and gene expression datasets were further mapped to the KEGG database to identify the molecular pathways that linked these genes together. Supervised hierarchical cluster analysis revealed 1,389 hypermethylated CpG sites and 22 hypomethylated CpG sites in cancer compared to the normal samples. Gene expression microarray analysis using a fold-change of at least 1.5 and a false discovery rate (FDR) at p>0.05 identified 404 upregulated and 463 downregulated genes in cancer samples. Integration of both datasets identified 51 genes with hypermethylation with low expression (negative association) and 13 genes with hypermethylation with high expression (positive association). Most of the overlapping genes belong to the focal adhesion and extracellular matrix-receptor interaction that play important roles in breast carcinogenesis. The present study displayed the value of using multiple datasets in the same set of tissues and how the integrative analysis can create a list of well-focused genes as well as to show the correlation between epigenetic changes and gene expression. These gene signatures can help us understand the epigenetic regulation of gene expression and could be potential targets for therapeutic intervention in the future.

Original languageEnglish
Pages (from-to)1959-1968
Number of pages10
JournalInternational Journal of Oncology
Volume45
Issue number5
DOIs
Publication statusPublished - 1 Nov 2014

Fingerprint

Genomics
Epigenomics
Carcinogenesis
Breast
Genes
DNA Methylation
Overlapping Genes
Methylation
Gene Expression
Breast Neoplasms
Focal Adhesions
DNA Fingerprinting
Neoplasm Genes
Gene Expression Regulation
Gene Expression Profiling
Microarray Analysis
Tumor Suppressor Genes
Oncogenes
Transcriptome
Cluster Analysis

Keywords

  • Breast cancer
  • CpG islands
  • DNA methylation
  • Epigenetics
  • Gene expression
  • Microarray

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Exploring breast carcinogenesis through integrative genomics and epigenomics analyses. / Mining, Chin; Mohd Mokhtar, Norfilza; Abdullah, Norlia; Muhammad, Rohaizak; Emran, Nor Aina; Md Ali, Siti Aishah; Harun, Roslan; A. Jamal, A. Rahman.

In: International Journal of Oncology, Vol. 45, No. 5, 01.11.2014, p. 1959-1968.

Research output: Contribution to journalArticle

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