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Promoter methylation of tumor suppressor genes in pre-neoplastic lesions; Potential marker of disease recurrence
- Source :
- Journal of Experimental & Clinical Cancer Research : CR
- Publication Year :
- 2014
-
Abstract
- Background: Epigenetic alterations of specific genes have been reported to be related to colorectal cancer (CRC) transformation and would also appear to be involved in the early stages of colorectal carcinogenesis. Little data are available on the role of these alterations in determining a different risk of colorectal lesion recurrence. The aim of the present study was to verify whether epigenetic alterations present in pre-neoplastic colorectal lesions detected by colonoscopy can predict disease recurrence. Methods. A retrospective series of 78 adenomas were collected and classified as low (35) or high-risk (43) for recurrence according to National Comprehensive Cancer Network guidelines. Methylation alterations were analyzed by the methylation-specific multiplex ligation probe assay (MS-MLPA) which is capable of quantifying methylation levels simultaneously in 24 different gene promoters. MS-MLPA results were confirmed by pyrosequencing and immunohistochemistry. Results: Higher levels of methylation were associated with disease recurrence. In particular, MLH1, ATM and FHIT gene promoters were found to be significantly hypermethylated in recurring adenomas. Unconditional logistic regression analysis used to evaluate the relative risk (RR) of recurrence showed that FHIT and MLH1 were independent variables with an RR of 35.30 (95% CI 4.15-300.06, P = 0.001) and 17.68 (95% CI 1.91-163.54, P = 0.011), respectively. Conclusions: Histopathological classification does not permit an accurate evaluation of the risk of recurrence of colorectal lesions. Conversely, results from our methylation analysis suggest that a classification based on molecular parameters could help to define the mechanisms involved in carcinogenesis and prove an effective method for identifying patients at high risk of recurrence.
- Subjects :
- Adult
Epigenomics
Male
Oncology
medicine.medical_specialty
Cancer Research
Carcinogenesis
Colorectal cancer
Colorectal adenoma
Biology
medicine.disease_cause
MLH1
Prognostic marker
FHIT
Internal medicine
Biomarkers, Tumor
medicine
Humans
Genes, Tumor Suppressor
Genetic Predisposition to Disease
Epigenetics
Aged
Retrospective Studies
Aged, 80 and over
Gene promoter methylation profile
Pre-neoplastic lesion classification
Risk of recurrence
Research
Cancer
DNA Methylation
Middle Aged
medicine.disease
DNA methylation
Neoplasm Recurrence, Local
Colorectal Neoplasms
Precancerous Conditions
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental & Clinical Cancer Research : CR
- Accession number :
- edsair.doi.dedup.....013ff3fcf1770680d9c1dbb1361d1b02