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P16 UV mutations in human skin epithelial tumors

Oncogene volume 18, pages 5477–5481 (1999)Cite this article

Abstract

The p16 gene expresses two alternative transcripts (p16α and p16β) 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 p16α and p16β), 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 : GG 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 p16β 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.

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Acknowledgements

This work was supported by grants from AP-HP, CERIES and GEFLUC. Nadem Soufir is a predoctoral fellowship of the Ligue Nationale contre le Cancer.

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Authors and Affiliations

  1. Institut de Recherche sur la Peau, Inserm U312, Hôpital Saint-Louis, Paris, France

    Nadem Soufir, Catherine Vilmer, Clara Moch, Louis Dubertret & Nicole Basset-Seguin

  2. Laboratoire de Dermatologie Moléculaire, IURC, Montpellier, France

    Jean Pierre Molès & Anne Tesniere

  3. Service d'Anatomopathologie, Hôpital Saint-Louis, Paris, France

    Olivier Verola & Jacqueline Rivet

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  1. Nadem Soufir
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Soufir, N., Molès, J., Vilmer, C. et al. P16 UV mutations in human skin epithelial tumors. Oncogene 18, 5477–5481 (1999). https://doi.org/10.1038/sj.onc.1202915

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