Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer

Détails

ID Serval
serval:BIB_53298DE57BAD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer
Périodique
Laboratory Investigation
Auteur⸱e⸱s
Burri  N., Shaw  P., Bouzourene  H., Sordat  I., Sordat  B., Gillet  M., Schorderet  D., Bosman  F. T., Chaubert  P.
ISSN
0023-6837 (Print)
Statut éditorial
Publié
Date de publication
02/2001
Volume
81
Numéro
2
Pages
217-29
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb
Résumé
The INK4a-ARF locus encodes two tumor suppressor proteins involved in cell-cycle regulation, p16INK4a and p14ARF, whose functions are inactivated in many human cancers. The aim of this study was to evaluate p14ARF and p16INK4a gene inactivation and its association with some clinocopathological parameters in colon cancer. The mutational and methylation status of the p14ARF and p16INK4a genes was analyzed in 60 primary colon carcinomas and 8 colon cancer cell lines. We have identified the first two reported mutations affecting exon 1beta of p14ARF in the HCT116 cell line and in one of the primary colon carcinomas. Both mutations occur within the N-terminal region of p14ARF, documented as important for nucleolar localization and interaction with Mdm2. Tumor-specific methylation of the p14ARF and p16INK4a genes was found in 33% and 32% of primary colon carcinomas, respectively. Methylation of the p14ARF was inversely correlated with p53 overexpression (p = 0.02). p14ARF and p16INK4a gene methylation was significantly more frequent in right-sided than in left-sided tumors (p = 0.02). Methylation of the p14ARF gene occurred more frequently in well-differentiated adenocarcinomas (p = 0.005), whereas the p16INK4a gene was more often methylated in poorly differentiated adenocarcinomas (p = 0.002). The present results underline the role of p14ARF and p16INK4a gene inactivation in the development of colon carcinoma. They suggest that the methylation profile of specific genes, in particular p14ARF and p16INK4a, might be related to biologically distinct subsets of colon carcinomas and possibly to different tumorigenic pathways.
Mots-clé
Carrier Proteins/*genetics Colon Colonic Neoplasms/*genetics Cyclin-Dependent Kinase Inhibitor p16 DNA Methylation DNA Primers Exons *Gene Silencing Genes, Tumor Suppressor Genes, p53 Humans Intestinal Mucosa/cytology/physiology *Mutation Neoplasm Proteins/genetics Nuclear Proteins Polymerase Chain Reaction Polymorphism, Single-Stranded Conformational Promoter Regions (Genetics) Proteins/*genetics Tumor Cells, Cultured Tumor Suppressor Protein p14ARF
Pubmed
Web of science
Création de la notice
28/01/2008 12:58
Dernière modification de la notice
20/08/2019 14:08
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