RESUMEN
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.
Asunto(s)
Proteínas de Ciclo Celular/genética , Ciclo Celular/genética , Eliminación de Gen , Genes cdc , Genes p16 , Genes p53/genética , Melanoma/genética , Mutación , Neoplasias Cutáneas/genética , Proteínas Supresoras de Tumor/genética , Inhibidor p15 de las Quinasas Dependientes de la Ciclina , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Análisis Mutacional de ADN , Homocigoto , HumanosRESUMEN
It is uncommon for a cancer to be diagnosed becauseof skin metastases. Cutaneous metastases as initialmanifestation of internal neoplasias, represent only0.8% of total cases and implies, in general, a very advancedgrade of the disease and short survival.When skin metastases of an unknown primary siteappear, lung cancer is the first option to be discardedin case of men, and breast cancer in case of women.Lung cancer spreads to the skin in 2.8-8.7% of thecases, in advanced phases of the disease, althoughjust in 7-23.8% of the cases, cutaneous metastasesappear as first manifestation of the primary tumor.Sometimes, a complete examination to discover thetumor reveals no metastases elsewhere
No disponible