Using data from the cancer genome atlas to analyse DNA methylation and copy number changes in the Y chromosome in male cancers

Many human cancers are more prevalent in men than women. This disparity is not fully explained by differences in key risk factor exposures, which suggests a possible genetic cause. Recent research has reported a link between loss of the Y chromosome (LoY) and increased incidence of non-haematological cancers. Using data from The Cancer Genome Atlas, I conducted an integrated, multi-‘omic analysis of Y chromosome methylation and copy number aberrations in three different cancers – colon, head and neck and kidney. My results indicate that aberrant methylation of the Y chromosome is common in all three cancer types. Hyper-methylation occurs in short, discrete regions, interspersed among wider regions of more general hypo-methylation. I also show that LoY is the most common aneuploidy in all three cancers, affecting between one third and one half of patients. Furthermore, both aberrant methylation and LoY are associated with reduced expression of potentially important genes. Most interestingly, for HPV negative head and neck cancer patients, I show a statistically significant association between LoY and worse survival, and that LoY may be linked to smoking. Subject to further validation, this suggests that LoY could be important in the pathogenesis of head and neck cancer for HPV negative patients