Methylome profiling reveals functions and genes which are differentially methylated in serrated compared to conventional colorectal carcinomaReportar como inadecuado




Methylome profiling reveals functions and genes which are differentially methylated in serrated compared to conventional colorectal carcinoma - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Clinical Epigenetics

, 7:101

Cancer epigenetics and diagnostics

Abstract

BackgroundSerrated adenocarcinoma SAC is a recently recognized colorectal cancer CRC subtype accounting for 7.5–8.7 % of CRCs. It has been shown that SAC has a worse prognosis and different histological and molecular features compared to conventional carcinoma CC but, to date, there is no study analysing its methylome profile.

ResultsThe methylation status of 450,000 CpG sites using the Infinium Human Methylation 450 BeadChip array was investigated in 103 colorectal specimens, including 39 SACs and 34 matched CCs, from Spanish and Finnish patients. Microarray data showed a higher representation of morphogenesis-, neurogenesis-, cytoskeleton- and vesicle transport-related functions and also significant differential methylation of 15 genes, including the iodothyronine deiodinase DIO3 and the forkhead family transcription factor FOXD2 genes which were validated at the CpG, mRNA and protein level using pyrosequencing, methylation-specific PCR, quantitative polymerase chain reaction qPCR and immunohistochemistry. A quantification study of the methylation status of CpG sequences in FOXD2 demonstrated a novel region controlling gene expression. Moreover, differences in these markers were also evident when comparing SAC with CRC showing molecular and histological features of high-level microsatellite instability.

ConclusionsThis methylome study demonstrates distinct epigenetic regulation patterns in SAC which are consistent to previous expression profile studies and that DIO3 and FOXD2 might be molecular targets for a specific histology-oriented treatment of CRC.

KeywordsSerrated carcinoma Colorectal cancer Methylome Microarray analysis FOXD2 DIO3 CpG island Pyrosequencing AbbreviationsCCconventional carcinoma

CpGcytosine-phospho-guanine

CRCcolorectal carcinoma

hMSI-Hcolorectal carcinoma showing typical molecular and histological features of MSI-H

IHCimmunohistochemistry

MSI-Hhigh-grade microsatellite instability

MSPmethylation-specific PCR

MSSmicrosatellite stability

qPCRquantitative polymerase chain reaction

SACserrated adenocarcinoma

SDstandard deviation

WHOWorld Health Organisation

Electronic supplementary materialThe online version of this article doi:10.1186-s13148-015-0128-7 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Autor: Pablo Conesa-Zamora - José García-Solano - María del Carmen Turpin - Patricia Sebastián-León - Daniel Torres-Moreno -

Fuente: https://link.springer.com/



DESCARGAR PDF




Documentos relacionados