Pan-cancer methylation and expression profiling of adenocarcinomas revealed epigenetic silencing in the WNT signaling pathway.

Adenocarcinomas are tumors of glandular characteristics. While tissues of common origins have been known to undergo similar epigenetic changes, it is unclear whether adenocarcinomas of different cancer types would exhibit similar DNA methylation and epigenetic regulation profiles. Herein, we studied global methylation and mRNA expression levels in 1214 lung, prostate, colon, and rectal cancer samples from The Cancer Genome Atlas (TCGA). We identified 602 candidate epigenetically silenced genes shared across these cancer types, and 835 associated CpG sites. The shared candidate genes are enriched in developmental processes. Specifically, 15 of these genes were found in the WNT signaling pathway (enrichment test p-value=1.53x10-6). Notably, the subset of silenced WNT pathway genes in each sample may be different, and both WNT activating or inhibiting genes could be suppressed. Clustering analysis showed that each tumor type contained a similar hyper-methylated subset of samples showing strong epigenetic silencing in the WNT pathway genes, and other fractions of samples expressing subset of the genes. Overall, our results showed that aberration in epigenetic regulation of the WNT signaling pathway is a common signature in adenocarcinomas.