Researchers Identify Breast Cancer Target Genes Via Fine-Mapping of Disease Risk Regions

An international team of researchers has identified 191 likely breast cancer target genes in 150 disease risk regions using a fine-mapping technique that analyzes gene expression, chromatin interaction, and functional annotations.

In a study published on Tuesday in Nature Genetics, the team noted that while GWAS studies have identified breast cancer risk variants in more than 150 genomic regions, the mechanisms underlying risk remain largely unknown. They aimed to fine-map all known breast cancer susceptibility regions using dense genotype data on more than 217,000 subjects participating in the Breast Cancer Association Consortium (BCAC) and the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

The study also revealed novel pathways, the researcher said, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling, the AP-2 transcription factors pathway, and regulation of IκB kinase/nuclear factor-κB (NF-κB) signaling, the last of which is specifically over-represented among ER-negative target genes. They also found significant over-representation of additional carcinogenesis-linked pathways, including cyclic adenosine monophosphate, NOTCH, phosphoinositide 3-kinase, RAS and WNT/β-catenin, and of receptor tyrosine kinase signaling, including fibroblast growth factor receptor, epidermal growth factor receptor and transforming growth factor-β receptor.

Source: https://www.genomeweb.com/cancer/researchers-identify-breast-cancer-target-genes-fine-mapping-disease-risk-regions