Promoter methylation of tumor suppressor genes in pre-neoplastic lesions; potential marker of disease recurrence.

Claudia Rengucci, Giulia De Maio, Andrea Casadei Gardini, Mattia Zucca, Emanuela Scarpi, Chiara Zingaretti, Giovanni Foschi, Maria Maddalena Tumedei, Chiara Molinari, Luca Saragoni, Maurizio Puccetti, Dino Amadori, Wainer Zoli, Daniele Calistri
J Exp Clin Cancer Res. 2014-08-05; 33(1):
DOI: 10.1186/s13046-014-0065-x

PubMed
Lire sur PubMed



1. J Exp Clin Cancer Res. 2014 Aug 5;33:65. doi: 10.1186/s13046-014-0065-x.

Promoter methylation of tumor suppressor genes in pre-neoplastic lesions;
potential marker of disease recurrence.

Rengucci C, De Maio G, Casadei Gardini A, Zucca M, Scarpi E, Zingaretti C, Foschi
G, Tumedei MM, Molinari C, Saragoni L, Puccetti M, Amadori D, Zoli W, Calistri D.

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.

DOI: 10.1186/s13046-014-0065-x
PMID: 25091577 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus