Deregulation of the tumour suppressor genes p14(ARF), p15(INK4b), p16(INK4a) and p53 in basal cell carcinoma.
BACKGROUND
Basal cell carcinoma (BCC) is a locally aggressive slowly growing tumour that rarely metastasizes and is mostly seen in older members of the population.


OBJECTIVE
To determine the involvement of the tumour suppressor genes p14(ARF), p15(INK4b), p16(INK4a) and p53 in BCC.


METHODS
We investigated the integrity of the CDKN2A locus in 15 BCC samples by analysing the presence of allelic imbalance/loss of heterozygosity (LOH). Moreover, we studied the mRNA expression levels of the tumour suppressor genes p14(ARF), p15(INK4b), p16(INK4a) and p53 in the BCC samples and compared them with mRNA levels in the corresponding normal tissue. The presence of mutations was examined by sequencing for exons 1a and 2 of p16(INK4a).


RESULTS
We found LOH in one BCC sample for the marker D9S1748. A polymorphism (G442A) of exon 2 was detected in three cases. p14(ARF), p15(INK4b) and p53 presented high expression levels, whereas p16(INK4a) exhibited low mRNA levels compared with the corresponding normal tissue. Significant correlations were detected among the genes studied.


CONCLUSIONS
Our results demonstrate a different expression profile between p16(INK4a) and p14(ARF), p15(INK4b) and p53 in BCC. Moreover, we found a low percentage of LOH and of a polymorphic sequence variant (Ala148Thr) for the CDKN2A locus.
Kanellou
P
P
University of Crete, Greece.
Zaravinos
A
A
Zioga
M
M
Spandidos
D A
DA
D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D019942:Genes, p16; D016158:Genes, p53; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics*; D013223:Statistics as Topic; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
D050762:Cyclin-Dependent Kinase Inhibitor p15; D012333:RNA, Messenger; D025803:Tumor Suppressor Protein p14ARF; D025521:Tumor Suppressor Proteins