|dc.description.abstract||Background: Altered methylation patterns are driving forces in colorectal carcinogenesis. The serrated adenocarcinoma
(SAC) and sporadic colorectal carcinoma showing histological and molecular features of microsatellite instability (hmMSIH)
are two endpoints of the so-called serrated pathological route sharing some characteristics but displaying a totally
different immune response and clinical outcome. However, there are no studies comparing the methylome of these two
subtypes of colorectal carcinomas. The methylation status of 450,000 CpG sites using the Infinium Human Methylation
450 BeadChip array was investigated in 48 colorectal specimens, including 39 SACs and 9 matched hmMSI-H.
Results: Microarray data comparing SAC and hmMSI-H showed an enrichment in functions related to morphogenesis,
neurogenesis, cytoskeleton, metabolism, vesicle transport and immune response and also significant differential
methylation of 1540 genes, including CD14 and HLA-DOA which were more methylated in hmMSI-H than in SAC
and subsequently validated at the CpG, mRNA and protein level using pyrosequencing, quantitative polymerase
chain reaction (qPCR) and immunohistochemistry.
Conclusions: These results demonstrate particular epigenetic regulation patterns in SAC which may help to
define key molecules responsible for the characteristic weak immune response of SAC and identify potential
targets for treating SAC, which lacks molecular targeted therapy.||spa