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PMID: 19384295 Published · ppublish English Evaluation Study Journal Article Research Support, Non-U.S. Gov't

Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease.

British journal of cancer ·Vol. 100 ·No. 10 ·2009-05-19 ·Pages 1534-9

Mayor R, Casadomé L, Azuara D, Moreno V, Clark SJ, Capellà G, Peinado MA

Abstract

Large chromosomal regions can be suppressed in cancer cells as denoted by hypermethylation of neighbouring CpG islands and downregulation of most genes within the region. We have analysed the extent and prevalence of long-range epigenetic silencing at 2q14.2 (the first and best characterised example of coordinated epigenetic remodelling) and investigated its possible applicability as a non-invasive diagnostic marker of human colorectal cancer using different approaches and biological samples. Hypermethylation of at least one of the CpG islands analysed (EN1, SCTR, INHBB) occurred in most carcinomas (90%), with EN1 methylated in 73 and 40% of carcinomas and adenomas, respectively. Gene suppression was a common phenomenon in all the tumours analysed and affected both methylated and unmethylated genes. Detection of methylated EN1 using bisulfite treatment and melting curve (MC) analysis from stool DNA in patients and controls resulted in a predictive capacity of, 44% sensitivity in positive patients (27% of overall sensitivity) and 97% specificity. We conclude that epigenetic suppression along 2q14.2 is common to most colorectal cancers and the presence of a methylated EN1 CpG island in stool DNA might be used as biomarker of neoplastic disease.

MeSH Terms
Adenoma/diagnosis,genetics,mortality,pathology Biomarkers, Tumor/analysis,genetics Carcinoma/diagnosis,genetics,mortality,pathology Chromosomes, Human, Pair 2 Colorectal Neoplasms/diagnosis,genetics,mortality,pathology CpG Islands/genetics DNA Methylation Epigenesis, Genetic/physiology Feces/chemistry Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Silencing/physiology Homeodomain Proteins/genetics Humans Inhibin-beta Subunits/genetics Molecular Diagnostic Techniques/methods Neoplasm Staging Prognosis Survival Analysis
Chemicals
Biomarkers, Tumor EN1 protein, human Homeodomain Proteins INHBB protein, human Inhibin-beta Subunits
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Mayor R
Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC), Badalona, Catalonia, Spain.
Casadomé L
Azuara D
Moreno V
Clark S J
Capellà G
Peinado M A
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
1532-1827
DOI
10.1038/sj.bjc.6605045
Published
2009-05-19
Epub
2009-00-21
Pages
1534-9
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2696749
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjc.6605045 PMC Full Text View journal details
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