Linking Cancer GWAS Risk Loci to Driver Genes via Co-Expression

The genetic background of skin cancer remains complex and challenging to integrate. Many somatic mutations within genes are known to cause and drive skin cancer, while genome-wide association studies (GWAS) have revealed numerous germline risk factors associated with the disease.

However, the overlap between known somatic driver genes and positional candidate genes from GWAS loci in skin cancer is surprisingly small.

Carlos G Urzúa-Traslaviña and the team aimed to determine if genes from multiple independent cancer GWAS loci exhibit tissue-specific co-regulation patterns converging on cancer-specific driver genes.

Researchers examined recent well-powered GWAS of breast, prostate, colorectal, and skin cancer by estimating gene co-expression and prioritizing genes significantly co-expressed with those within susceptibility loci from cancer GWAS.

They found that the prioritized genes were strongly enriched for cancer drivers as defined by COSMIC, IntOGen, and Dietlein et al. This enrichment was most significant when using co-expression networks derived from non-cancer samples of the relevant tissue of origin.

The study demonstrated how genes within cancer GWAS risk loci are connected to known cancer driver genes via tissue-specific co-expression networks.

This sheds light on why seemingly disparate gene sets, housing germline risk factors or somatic mutations, can lead to the same disease type.

P.D. support was provided by Dutch Research Council, L.F. was supported by a grant from the NWO and through a Senior Investigator Grant from the Oncode Institute and a grant from Saxum Volutum (Pericode).

Source: https://pubmed.ncbi.nlm.nih.gov/39010058/

Urzúa-Traslaviña CG, van Lieshout T, Boulogne F, et al. (2024). “Co-expression in tissue-specific gene networks links genes in cancer-susceptibility loci to known somatic driver genes.” BMC Med Genomics. 2024;17(1):186. Published 2024 Jul 15. doi:10.1186/s12920-024-01941-4