Loss of heterozygosity on chromosome 13q12-q14, BRCA-2 mutations and lack of BRCA-2 promoter hypermethylation in sporadic epithelial ovarian tumors

Esther Gras, Joan Cortes, Orland Diez, Carmen Alonso, Xavier Matias-Guiu, Montserrat Baiget, Jaime Prat

Producción científica: Contribución a una revistaArtículoInvestigaciónrevisión exhaustiva

49 Citas (Scopus)

Resumen

BACKGROUND. BRCA-1 and BRCA-2 are tumor suppressor genes in familial breast-ovarian carcinoma syndrome. BRCA-1 is also a tumor suppressor gene in sporadic ovarian carcinomas. However, the role of BRCA-2 in sporadic ovarian tumors remains unclear. METHODS. DNA from 52 patients with clinically apparent sporadic ovarian tumors was extracted from blood and from fresh-frozen tumor tissue and normal tissue (10 benign, 7 borderline, and 35 malignant). Loss of heterozygosity (LOH) was analyzed in six microsatellite loci on chromosome 13q. BRCA-2 mutations were detected by single-strand conformation polymorphism analysis and the protein truncation test. BRCA-2 promoter methylation was evaluated by methylation specific polymerase chain reaction analysis. RESULTS. LOH on chromosome 13q12-q14 was identified in 16 tumors (30.8%): Fifteen of these tumors were carcinomas (15 of 35 tumors; 42.8%) and one was a borderline tumor. LOH was frequent in carcinomas with serous differentiation (12 of 16 tumors; 75%). LOH on chromosome 13q12-q14 coexisted with LOH on chromosome 17q in 10 carcinomas. BRCA-2 methylation was not detected in any tumor. BRCA-2 mutations were found in three tumors (one somatic nonsense and two germline frameshift). BRCA-2 fulfilled the two hits for a tumor suppressor gene in these three tumors; in one of them, a BRCA-1 tumor suppressor role had been demonstrated previously. CONCLUSIONS. The results suggest that BRCA-1 and BRCA-2 may act synergically in sporadic ovarian carcinomas with serous differentiation. The demonstration of BRCA-2 germline mutations in patients with ovarian carcinoma with LOH on chromosome 13q12-q14 and lack of a remarkable family history of cancer suggest that the proportion of ovarian carcinomas that result from hereditary predisposition may be higher than previously estimated. © 2001 American Cancer Society.
Idioma originalInglés
Páginas (desde-hasta)787-795
PublicaciónCancer
Volumen92
N.º4
DOI
EstadoPublicada - 15 ago 2001

Huella

Profundice en los temas de investigación de 'Loss of heterozygosity on chromosome 13q12-q14, BRCA-2 mutations and lack of BRCA-2 promoter hypermethylation in sporadic epithelial ovarian tumors'. En conjunto forman una huella única.

Citar esto