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Tumour-specific methylation of PTPRG intron 1 locus in sporadic and Lynch syndrome colorectal cancer
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Tumour-specific methylation of PTPRG intron 1 locus in sporadic and Lynch syndrome colorectal cancer
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Tumour-specific methylation of PTPRG intron 1 locus in sporadic and Lynch syndrome colorectal cancer
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Journal Article
Tumour-specific methylation of PTPRG intron 1 locus in sporadic and Lynch syndrome colorectal cancer
2011
Overview
DNA methylation is a hallmark in a subset of right-sided colorectal cancers. Methylation-based screening may improve prevention and survival rate for this type of cancer, which is often clinically asymptomatic in the early stages. We aimed to discover prognostic or diagnostic biomarkers for colon cancer by comparing DNA methylation profiles of right-sided colon tumours and paired normal colon mucosa using an 8.5 k CpG island microarray. We identified a diagnostic CpG-rich region, located in the first intron of the protein-tyrosine phosphatase gamma gene (
PTPRG
) gene, with altered methylation already in the adenoma stage, that is, before the carcinoma transition. Validation of this region in an additional cohort of 103 sporadic colorectal tumours and 58 paired normal mucosa tissue samples showed 94% sensitivity and 96% specificity. Interestingly, comparable results were obtained when screening a cohort of Lynch syndrome-associated cancers. Functional studies showed that
PTPRG
intron 1 methylation did not directly affect
PTPRG
expression, however, the methylated region overlapped with a binding site of the insulator protein CTCF. Chromatin immunoprecipitation (ChIP) showed that methylation of the locus was associated with absence of CTCF binding. Methylation-associated changes in CTCF binding to
PTPRG
intron 1 could have implications on tumour gene expression by enhancer blocking, chromosome loop formation or abrogation of its insulator function. The high sensitivity and specificity for the
PTPRG
intron 1 methylation in both sporadic and hereditary colon cancers support biomarker potential for early detection of colon cancer.
Publisher
Springer International Publishing,Nature Publishing Group
Subject
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Chromatin Immunoprecipitation
/ Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis
/ Colorectal Neoplasms, Hereditary Nonpolyposis - genetics
/ Fundamental and applied biological sciences. Psychology
/ Gastroenterology. Liver. Pancreas. Abdomen
/ Gene Expression Regulation, Neoplastic
/ General aspects. Genetic counseling
/ Genetics of eukaryotes. Biological and molecular evolution
/ Humans
/ Introns
/ Molecular and cellular biology
/ Receptor-Like Protein Tyrosine Phosphatases, Class 5 - genetics
/ Repressor Proteins - genetics
/ Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
/ Tumors
