Mutation and homozygous deletion analyses of genes that control the G1/S transition of the cell cycle in skin melanoma: p53, p21, p16 and p15.

INTRODUCTION: The role of genes involved in the control of progression from the G1 to the S phase of the cell cycle in melanoma tumors is not fully known. MATERIAL AND METHODS: The aims of our study were to analyse alterations in p53, p21, p16 and p15 genes in melanoma tumors and melanoma cell lines by single strand conformational polymorphism (SSCP), and to detect homozygous deletions. We analysed the DNA from 39 patients with primary and metastatic melanomas, and from 9 melanoma cell lines. RESULTS: The SSCP technique showed heterozygous defects in the p53 gene in 8 of 39 (20.5%) melanoma tumors: three point mutations in intron sequences (introns 1 and 2) and exon 10, and three new polymorphisms located in introns 1 and 2 (C to T transition at position 11701 in intron 1; C insertion at position 11818 in intron 2; and C insertion at position 11875 in intron 2). One melanoma tumor exhibited two heterozygous alterations in the p16 exon 1 (stop codon and missense mutation). No defects were found in the remaining genes. Homozygous deletions were more frequent in melanoma cell lines than in melanoma tumors in p21, p16 and p15 (22.2%, 44.4%, and 44.4% versus 7.7%, 2.5%, and 5.1% respectively). TP53 did not show homozygous deletions. CONCLUSIONS: Our results suggest that these genes are involved in melanoma tumorigenesis; but perhaps not in the major targets. Other suppressor genes that may be informative of the mechanism of tumorigenesis in skin melanomas need to be studied.