Methylation Silencing and Mutations of the p14ARF and p16INK4a Genes in Colon Cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2001-02-01

AUTHORS

Nathalie Burri, Phillip Shaw, Hanifa Bouzourene, Isabelle Sordat, Bernard Sordat, Michel Gillet, Daniel Schorderet, Fred T Bosman, Pascal Chaubert

ABSTRACT

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 1β 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. More... »

PAGES

217-229

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/labinvest.3780230

DOI

http://dx.doi.org/10.1038/labinvest.3780230

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1014783955

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11232644


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58 colon carcinoma
59 development
60 different tumorigenic pathways
61 distinct subsets
62 exon 1β
63 function
64 gene inactivation
65 gene methylation
66 genes
67 human cancers
68 inactivation
69 interaction
70 left-sided tumors
71 lines
72 localization
73 loci
74 methylation
75 methylation profiles
76 methylation status
77 mutations
78 nucleolar localization
79 overexpression
80 p14ARF
81 p14ARF gene
82 p16INK4A gene
83 p16INK4A gene methylation
84 p16INK4a
85 p16INK4a gene inactivation
86 p53 overexpression
87 parameters
88 pathway
89 present results
90 primary colon carcinoma
91 profile
92 protein
93 region
94 regulation
95 results
96 role
97 role of p14ARF
98 silencing
99 specific genes
100 status
101 study
102 subset
103 suppressor protein
104 tumor suppressor protein
105 tumor-specific methylation
106 tumorigenic pathways
107 tumors
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