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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.
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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
BACKGROUND AND OBJECTIVE: Cystinosis is an autosomal recessive disorder characterized by an accumulation of intralysosomal cystine. Three disease forms exist, infantile, juvenile or late-onset, and ocular nonnephropathic cystinosis, delineated on the basis of severity of symptoms and age of onset. The knowledge of early clinic manifestations and the onset of the appropriate therapy delay the evolution of the disease and improve the general conditions. Therefore, it is necessary to develop a sensible diagnostic method for early detection and treatment of the disease. CLINICAL CASE AND METHODS: The leukocyte cystine content was determined by HPLC in a 42 years old female patient after renal transplantation, and with the clinical characteristic complications of the intermediate cystinosis. Equally, the molecular characterization of the structural defects of the cystinosin (CTNS) gene was made in the patient and in all family members. RESULTS: By measuring of the leukocyte cystine content in the patient and family members, we have determined 5 family members as heterozygous. This result was confirmed by molecular analysis that showed the approximately 65 kb deletion in the 5 family members. The patient was heterozygous for the approximately 65 kb deletion, and the second alteration was not determined. CONCLUSIONS: We presented a useful diagnostic method, based in the determination of cystine content of polymorphonuclear leukocytes, which permits to detect the heterozygous individuals.
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Cistina/sangre , Cistinosis/diagnóstico , Leucocitos/química , Adulto , Sistemas de Transporte de Aminoácidos Neutros , Cromatografía Líquida de Alta Presión , Femenino , Tamización de Portadores Genéticos , Glicoproteínas/genética , Humanos , Proteínas de la Membrana/genética , Proteínas de Transporte de Membrana , LinajeRESUMEN
No disponible
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Femenino , Humanos , Genes erbB-2 , Neoplasias de la Mama/diagnóstico , Reacción en Cadena de la Polimerasa , Hibridación Fluorescente in SituRESUMEN
No disponible