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Aberrant methylation of the CDKN2a/p16 INK4a gene promoter region in preinvasive bronchial lesions: A prospective study in high‐risk patients without invasive cancer.
Author(s) -
Lamy Aude,
Sesboüé Richard,
Bourguig Jeannette,
Dautréaux Brigitte,
Métayer Josette,
Frébourg Thierry,
Thiberville Luc
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10474
Subject(s) - cdkn2a , methylation , dna methylation , epigenetics , lung cancer , field cancerization , biology , cancer research , cancer , pathology , cpg site , malignant transformation , medicine , gene , gene expression , genetics
Among the identified factors involved in malignant transformation, abnormal methylation of the CDKN2A/p16 INK4a gene promoter has been described as an early event, particularly in bronchial cell cancerization. Precancerous bronchial lesions ( n = 70) prospectively sampled during fluorescence endoscopy in a series of 37 patients at high risk for lung cancer were studied with respect to the methylation status of the CDKN2A gene. Methylation‐specific polymerase chain reaction was performed on DNA extracted from pure bronchial cell populations derived from biopsies and detection of p16 protein was studied by immunohistochemistry on contiguous parallel biopsies. Aberrant methylation of the CDKN2A gene promoter was found in 19% of preinvasive lesions and its frequency increased with the histologic grade of the lesions. Methylation in at least 1 bronchial site was significantly more frequent in patients with cancer history, although there was no difference in the outcome of patients with or without methylation in bronchial epithelium. The other risk factors studied (tobacco and asbestos exposure) did not influence the methylation status. There was no relationship between CDKN2A methylation and the evolutionary character of the lesions. Our results confirm that abnormal methylation of the CDKN2A gene promoter is an early event in bronchial cell cancerization, which can persist for several years after carcinogen exposure cessation, and show that this epigenetic alteration cannot predict the evolution of precancerous lesions within a 2‐year follow‐up. © 2002 Wiley‐Liss, Inc.