Cancers

Background. The typical methylation patterns associated with cancer are
\nhypermethylation at gene promoters and global genome hypomethylation. Aberrant CpG island
\nhypermethylation at promoter regions and global genome hypomethylation have not been
\nassociated with histological colorectal carcinomas (CRC) subsets. Using Illumina’s 450 k Infinium
\nHuman Methylation beadchip, the methylome of 82 CRCs were analyzed, comprising different
\nhistological subtypes: 40 serrated adenocarcinomas (SAC), 32 conventional carcinomas (CC) and 10
\nCRCs showing histological and molecular features of microsatellite instability (hmMSI‐H), and,
\nadditionally, 35 normal adjacent mucosae. Scores reflecting the overall methylation at 250 bp, 1 kb
\nand 2 kb from the transcription starting site (TSS) were studied. Results. SAC has an intermediate
\nmethylation pattern between CC and hmMSI‐H for the three genome locations. In addition, the shift
\nfrom promoter hypermethylation to genomic hypomethylation occurs at a small sequence between
\n250 bp and 1 Kb from the gene TSS, and an asymmetric distribution of methylation was observed
\nbetween both sides of the CpG islands (N vs. S shores). Conclusion. These findings show that
\ndifferent histological subtypes of CRC have a particular global methylation pattern depending on
\nsequence distance to TSS and highlight the so far underestimated importance of CpGs aberrantly
\nhypomethylated in the clinical phenotype of CRCs.