Mutational analysis of CDKN2A genes in patients with squamous cell carcinoma of the skin

Z Saridaki, T Liloglou, A Zafiropoulos, E Koumantaki, O Zoras, D A Spandidos

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46 Citations (Scopus)


BACKGROUND: Nonmelanoma skin cancers [squamous cell carcinomas (SCC) and basal cell carcinomas (BCC)] are the most common neoplasias of the Caucasian population.

OBJECTIVES: The purpose of our study was to determine the involvement of CDKN2A genes in the development of sporadic nonmelanoma skin cancer in Greek patients.

PATIENTS AND METHODS: Allelic imbalance analysis was performed in 22 SCC and five Bowen's disease specimens. Mutational analysis was performed on exons 1alpha, 1beta and 2 of the CDKN2A locus in 22 SCC, five Bowen's disease and 39 BCC specimens. Exon 1alpha was additionally screened in 28 BCC specimens to complete the mutational analysis of a previous study.

RESULTS: Overall, 52% (14 of 27) of the SCC and Bowen's disease specimens exhibited loss of heterozygosity (LOH) in at least one microsatellite marker, whereas, only two of 27 (7%) exhibited microsatellite instability. LOH in 9p appears to be equally involved in both BCC and SCC tumours. Exons 1alpha, 1beta and 2 of the CDKN2A locus were screened for mutations. A Val28Gly substitution in exon 1alpha and a CCC-->TTT (Ala57Val and Arg58Ter) substitution in exon 2, resulting in a change in the amino acid sequence, are reported for the first time in two SCCs, the latter being indicative of a combination of an ultraviolet (UV) radiation-induced mutation and a point mutation. A previously described polymorphism of CDKN2A, the gene for p16INK4a, Ala148Thr, was also detected in an allelic frequency of 3.72%. No mutation was found in any of the five Bowen's disease specimens, or in exon 1beta of CDKN2A, also the gene for p14ARF.

CONCLUSIONS: Mutations and the high incidence of 9p LOH detected in our SCC samples imply that inactivation of CDKN2A genes, via allelic loss and/or mutation (probably UV-induced) may play a significant role in nonmelanoma skin cancer development, particularly in the more aggressive SCC type.

Original languageEnglish
Pages (from-to)638-48
Number of pages11
JournalThe British journal of dermatology
Issue number4
Publication statusPublished - 1 Apr 2003


  • Adult
  • Aged
  • Aged, 80 and over
  • Bowen's Disease/genetics
  • Carcinoma, Basal Cell/genetics
  • Carcinoma, Squamous Cell/genetics
  • DNA Mutational Analysis
  • DNA, Neoplasm/genetics
  • Female
  • Genes, p16
  • Humans
  • Loss of Heterozygosity
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Mutation
  • Polymorphism, Single-Stranded Conformational
  • Skin Neoplasms/genetics


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