@article{3083390,
    title = "Mutational analysis of CDKN2A genes in patients with squamous cell
carcinoma of the skin",
    author = "Saridaki, Z and Liloglou, T and Zafiropoulos, A and Koumantaki, E and and Zoras, O and Spandidos, DA",
    journal = "British Journal of Dermatology",
    year = "2003",
    volume = "148",
    number = "4",
    pages = "638-648",
    publisher = "Wiley",
    issn = "0007-0963, 1365-2133",
    doi = "10.1046/j.1365-2133.2003.05230.x",
    keywords = "allelic imbalance; mutation; p16; CDKN2A gene; skin cancer",
    abstract = "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 p16(INK4a) , 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 p14(ARF) .
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."
}