The integration of transcriptome and epigenome in the association of mosaic loss of chromosome Y (mLOY) and cancer

Abstract

It has been demonstrated that mosaic loss of chromosome Y (mLOY) is associated with aging and age-related disease such as cancer [1, 2] or Alzheimer's disease [3]. However, the integrate mechanisms of gene expression and methylation of mLOY have been poorly evaluated to date. In order to ll this gap, a total of 9.927 samples belonging to The Cancer Genome Atlas project were analyzed. LOY status was inferred from SNP-array data using our MADloy tool [4]. Association analysis revealed that the pooled odds ratio (OR) of association between mLOY and tumor samples was 8.04 (CI95% 4.60 { 14.06). Di erences in the magnitude of the OR were observed across cancer types, with no association with prostate cancer and high association with kidney tumor. Transcriptomic data analysis showed that only genes in chromosome Y were down-regulated having strong e ect in kidney, bladder and lung cancer. Epigenomic studies provided a large list of CpGs associated with LOY in Y chromosome as well as in autosomes. Gene enrichment analysis revealed a range of pathways involved in mLOY that vary across tumors. These include biosynthetic and metabolic processes, demethylation and immune response. In summary, we have established an unavoidable association between mosaic LOY events and cancer, adding the association of both, transcriptome and epigenome.