TY - JOUR
TI - High frequency of loss of heterozygosity on chromosome region 9p21-p22
but lack of p16(INK4a)/p19(ARF) mutations in Greek patients with basal
cell carcinoma of the skin
AU - Saridaki, Z
AU - Koumantaki, E
AU - Liloglou, T
AU - Sourvinos, G and
AU - Papadopoulos, O
AU - Zoras, O
AU - Spandidos, DA
JO - Journal of Investigative Dermatology
PY - 2000
VL - 115
TODO - 4
SP - 719-725
PB - BLACKWELL SCIENCE PUBL INC CAMBRIDGE
SN - 0022-202X, 1523-1747
TODO - 10.1046/j.1523-1747.2000.00098.x
TODO - basal cell carcinoma skin cancer; mutations; p16 genes; p19 genes
TODO - Basal cell carcinoma of the skin is the most common neoplasia in humans.
Previous studies have shown the existence of allelic imbalance (loss of
heterozygosity and microsatellite instability) in BCC on several human
chromosomes. Chromosome region 9p21-p22 harbors the CDKN2a/16(INK4a),
p19(ARF), and p15(INK4b) tumor suppressor genes. To determine the
contribution of these genes to the development of basal cell carcinomas
we looked for evidence of allelic imbalance in 67 sporadic basal cell
carcinoma specimens from Greek patients and screened 28 of them
presenting loss of heterozygosity at 9p21-p22 for germline mutations in
p16(INK4a) and p19(ARF) genes. Chromosome regions 17q21 and 17p13 were
also screened for allelic imbalance in all the 67 basal cell carcinoma
specimens. Overall, 69% (46 of 67) of the specimens displayed loss of
heterozygosity in at least one microsatellite marker, whereas only six
of the 67 (9%) exhibited microsatellite instability. For the 9p21-p22
locus the overall frequency of loss of heterozygosity reached 55% (37
of 67) and is the highest reported. The overall frequency of loss of
heterozygosity for the 17q21 locus is 34% (22 of 64) and for the 17p13
locus is 11% (seven of 65). Two of the 28 loss of heterozygosity
positive cases were heterozygous for a previously described
polymorphism, Ala148Thr, in exon 2 of the CDKN2a gene. This is the first
demonstration of polymorphism in the CDKN2a gene in human basal cell
carcinomas. No sequence variation in exon 1 beta of the p19(ARF) gene
was found. Our results provide evidence of a significantly high
occurrence of loss of heterozygosity for the 9p21-p22 locus; however,
lack of p16(INK4a)/p19(ARF) mutation suggests that these genes seem not
to be implicated by mutational inactivation in the development of basal
cell carcinoma. Other(s), yet unidentified, tumor suppressor gene(s)
located in this locus may be related to this specific type of skin
cancer.
ER -