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P16UV mutations in human skin epithelial tumors
Author(s): Soufir N, Moles JP, Vilmer C, Moch C, Verola O, Rivet J, Tesniere A, Dubertret L, Basset-Seguin N
Source: ONCOGENE    Volume: 18    Issue: 39    Pages: 5477-5481    Published: SEP 23 1999  
Times Cited: 57     References: 48     
Abstract: The p16 gene expresses two alternative transcripts (p16 alpha and p16 beta) involved in tumor suppression via the retinoblastoma (Rb) or p53 pathways. Disruption of these pathways can occur through inactivation of p16 or p53, or activating mutations of cyclin dependant kinase 4 gene (Cdk4). We searched for p16, Cdk4 and p53 gene mutations in 20 squamous cell carcinomas (SSCs), 1 actinic keratosis (AK), and 28 basal cell carcinomas (BCCs), using PCR-SSCP. A deletion and methylation analysis of p16 was also performed. Six different mutations (12%) were detected in exon 2 of p16 (common to p16 alpha and p16 beta), in five out of 21 squamous lesions (24%) (one AK and four SCCs) and one out of 28 BCCs (3.5%), These included four (66%) ultraviolet (UV)-type mutations (two tandems CC : GC to TT : AA transitions and two C : G to T : A transitions at dipyrimidic site) and two transversions, P53 mutations were present in 18 samples (37%), mostly of UV type. Of these, only two (one BCC and one AK) harboured simultaneously mutations of p16, but with no consequence on p16 beta transcript. Our data demonstrate for the first time the presence of p16 UV induced mutations in non melanoma skin cancer, particularly in the most aggressive SCC type, and support that p16 and p53 are involved in two independent pathways in skin carcinogenesis.
Document Type: Article
Language: English
Reprint Address: Basset-Seguin, N (reprint author), Hop St Louis, Inst Rech Peau, INSERM, U312, Pavillon Bazin,1 Ave Claude Vellefaux, F-75010 Paris, France
Addresses:
1. Hop St Louis, Inst Rech Peau, INSERM, U312, F-75010 Paris, France
2. IURC, Lab Dermatol Mol, Montpellier, France
3. Hop St Louis, Serv Anatomopathol, Paris, France
Publisher: STOCKTON PRESS, HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
Subject Category: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity
IDS Number: 238PL
ISSN: 0950-9232
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