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P16 UV mutations in human skin epithelial tumors
N Soufir1, J P Molès, C Vilmer
1Institut de Recherche sur la Peau, Inserm U312, Hôpital Saint-Louis, Paris, France.
Oncogene
|September 28, 1999
Summary
This study found ultraviolet-induced mutations in the p16 gene in skin cancers like squamous cell carcinoma. These p16 gene mutations, along with p53 gene mutations, suggest independent roles in skin cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- The p16 gene is a tumor suppressor involved in regulating cell growth via the retinoblastoma (Rb) or p53 pathways.
- Disruptions in these critical tumor suppressor pathways, through p16 or p53 inactivation or Cdk4 activation, are implicated in cancer development.
- Non-melanoma skin cancers, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), represent a significant public health concern.
Purpose of the Study:
- To investigate the presence and types of mutations in the p16, Cdk4, and p53 genes in various non-melanoma skin cancers.
- To determine the potential role of ultraviolet (UV) radiation in inducing mutations within these key cancer-related genes.
- To elucidate the relationship between p16 and p53 pathway alterations in the pathogenesis of skin carcinogenesis.
Main Methods:
- Analysis of p16, Cdk4, and p53 gene mutations in 20 SCCs, 1 actinic keratosis (AK), and 28 BCCs using Polymerase Chain Reaction-Single Strand Conformation Polymorphism (PCR-SSCP).
- Performed deletion and methylation analysis for the p16 gene.
- Characterized mutation types, including UV-signature mutations, and assessed co-occurrence of p16 and p53 mutations.
Main Results:
- Six distinct mutations (12% overall) were identified in exon 2 of the p16 gene in 24% of squamous lesions (1 AK, 4 SCCs) and 3.5% of BCCs.
- A significant proportion (66%) of p16 mutations were UV-type, indicating UV radiation as a likely mutagenic factor.
- p53 mutations were found in 37% of samples, predominantly UV-type. Co-occurring p16 and p53 mutations were rare (2 samples) and did not affect the p16beta transcript.
Conclusions:
- This study provides the first evidence of UV-induced p16 gene mutations in non-melanoma skin cancer, particularly in aggressive SCC.
- The findings support the involvement of p16 and p53 in independent pathways during skin carcinogenesis.
- Alterations in the p16 gene may play a crucial role in the development of UV-associated skin cancers.