RESUMEN
BACKGROUND: The frequency and the type of BRCA1 mutations vary widely and might have different geographic and ethnic distribution. Most of these alterations are generally found in isolated populations as a consequence of the founder effect. The object of this study was to determine whether 4843delC, a deleterious mutation of the BRCA1 gene, might be due to a founder effect originating in the Sicilian region of Italy. This mutation was described by us for the first time and identified in two unrelated Sicilian families with hereditary breast/ovarian cancer. The two families were from the same geographical area (south-western area of Palermo, Sicily). The homogeneity of the ethnic group of the two families and the Single Nucleotide Polymorphism (SNPs) analysis of probands led us to perform a study of the allelotype of the various members. PATIENTS AND METHODS: The analysis of the haplotype of the probands and of several family members was conducted by means of a study of the highly polymorphic microsatellites within or flanking the BRCA1 gene. RESULTS: This analysis revealed the presence of a common allele associated with the mutation. CONCLUSIONS: We therefore conclude that 4843delC of the BRCA1 gene is a possible founder mutation in the Sicilian population.
Asunto(s)
Análisis Mutacional de ADN , Efecto Fundador , Eliminación de Gen , Genes BRCA1 , Neoplasias de la Mama/genética , Femenino , Haplotipos , Humanos , Masculino , Repeticiones de Microsatélite , Neoplasias Ováricas/genética , Linaje , SiciliaRESUMEN
BACKGROUND: Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations CONCLUSIONS: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques.
Asunto(s)
Neoplasias Colorrectales/genética , Metilación de ADN , Genes p16 , Genes p53 , Genes ras , Anciano , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , ADN de Neoplasias/sangre , ADN de Neoplasias/genética , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Pronóstico , Regiones Promotoras Genéticas , Estudios ProspectivosRESUMEN
This report describes the case of a 70-year-old female suffering from diabetes mellitus and dilatative cardiomyopathy with congestive heart failure. It is likely that alveolar-capillary membrane damage occurred apart from cardiac involvement. Diffuse interstitial pulmonary fibrosis subsequently occurred with consequent acute progressive respiratory failure and death. The cause of the damage to the alveolar-capillary membranes is still unknown and we thought that long-term administration of captopril might have contributed to the damage itself, since like all ACE-inhibitors, captopril is able to bring about tissular storage of both bradykinin and prostaglandins and therefore alter the pulmonary reactivity to phlogistic stimuli.