Exploring breast carcinogenesis through integrative genomics and epigenomics analyses.

Area of Science:

• Genomics and Epigenetics
• Cancer Biology
• Molecular Pathology

Background:

• DNA methylation alterations are implicated in breast cancer, but links to gene expression are underexplored.
• Limited data exists from Asian populations, highlighting a need for regional epigenetic and transcriptomic analysis.
• Understanding epigenome-transcriptome correlations is crucial for identifying breast cancer drivers and therapeutic targets.

Purpose of the Study:

• To investigate DNA methylation patterns and gene expression profiles in primary breast tumors from an Asian cohort.
• To correlate epigenetic modifications with gene expression changes and identify associated molecular pathways.
• To discover potential gene signatures and therapeutic targets for breast cancer.

Main Methods:

• DNA methylation profiling using Illumina Infinium HumanMethylation27 BeadChip on 76 tumor and 25 normal tissues.
• Gene expression profiling via Affymetrix GeneChip Human Gene 1.0 ST array on 15 tumor and 5 normal tissues.
• Integrative analysis of methylation and expression data, pathway mapping using KEGG database.

Main Results:

• Identified 1,389 hypermethylated and 22 hypomethylated CpG sites in cancer versus normal samples.
• Detected 404 upregulated and 463 downregulated genes in cancer samples.
• Found 51 genes with hypermethylation and low expression (negative association) and 13 with hypermethylation and high expression (positive association), notably in focal adhesion and ECM-receptor interaction pathways.

Conclusions:

• Integrative analysis of epigenome and transcriptome data in the same tissues provides focused gene signatures.
• Epigenetic changes correlate with gene expression, offering insights into breast cancer's molecular regulation.
• Identified gene signatures represent potential targets for future breast cancer therapeutic interventions.