Two Major Dysregulated Functions Identified in Inflammatory Breast Cancer

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(ChemotherapyAdvisor) – Genome-wide microarray analyses of copy number variation (CNV) and gene expression have identified two major dysregulated functions in inflammatory breast cancer: survival regulation via Rac/PAK as well as the PTEN/PI3K/AKT signaling pathways, results of a study presented during the 2013 Breast Cancer Symposium in San Francisco, CA has found.

These genes and pathways may serve as prognostic markers for patients with inflammatory breast cancer by integrating gene expression profiles and copy number variations, reported Mian Xie, MD, PhD, Deputy Physician in Chief, Guangzhou Medical University, Guangzhou, China.

Noting that inflammatory breast cancer is poorly defined at the molecular level, Dr. Xie and colleagues sought to identify genes reproducibly associated with survival in patients with this aggressive form of the disease. They analyzed 56 pairs of breast cancer tissue and normal tissue from patients with inflammatory breast cancer using Affymetrix SNP 6.0 and Affymetrix U133 plus 2.0 microarrays.

“To investigate genomic alterations, we used an Affymetrix Genome-Wide Human SNP 6.0 array containing 1.8 million SNP (single nucleotide polymorphism) and CNV probes in total,” the investigators reported. These data were then imported into the Partek Genomic Suite for CNV analysis and ingenuity Pathway Analysis was conducted to describe gene-gene interaction networks and canonical pathways.

In at least 35% of samples, the genomic landscape of frequent CNV regions (CNVRs) was revealed. “Further statistical analysis for genes located in the CNVRs identified 387 genes differentially expressed between tumor and normal tissues (P<0.001),” they reported.

Elevated Pearson correlation coefficients demonstrated concordance between copy number variations and gene expression changes. Among the 387 copy number variation-driven genes, Fisher's exact test identified five canonical pathways that were significantly enriched.

“Further validation using three independent cohorts demonstrated prediction of survival,” they concluded.

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