Mutational analyses of RB and BRCA2 as candidate tumour suppressor genes in parathyroid carcinoma.
Clin Endocrinol (Oxf)
; 59(2): 180-9, 2003 Aug.
Article
em En
| MEDLINE
| ID: mdl-12864795
ABSTRACT
OBJECTIVE:
Strong evidence indicates that at least one key tumour suppressor gene important for the development of malignant parathyroid tumours is located on chromosome 13, but the critical target gene remains unknown. Importantly, the region of acquired DNA loss includes two established tumour suppressor genes, the retinoblastoma gene, RB (RB1) and BRCA2. Resolution of whether RB or BRCA2 is the critical 13q tumour suppressor gene in parathyroid cancer requires analysis of these genes' sequences for intragenic inactivating mutations. Therefore, RB and BRCA2 were analysed in a group of parathyroid carcinomas in which mutations of these genes should be most readily detectable. PATIENTS ANDDESIGN:
Six parathyroid carcinomas from four patients which showed loss of heterozygosity (LOH) at the RB locus and/or 13q loss by comparative genomic hybridazation (CGH) were selected from a CGH/LOH-screened panel of 16 carcinoma specimens from 10 patients. These tumours were examined for mutations by direct sequencing of the complete 27-exon coding region, intron-exon boundaries and promoter of RB. The 26 coding exons and intron-exon boundaries of BRCA2 were also directly sequenced in seven parathyroid carcinomas with loss in the BRCA2 region.RESULTS:
No microdeletions, insertions, or point mutations were detected in either RB or BRCA2 in any of the carcinomas.CONCLUSION:
The absence of tumour-specific somatic mutations in RB and BRCA2 suggests that they are unlikely to act as classic tumour suppressor genes in the pathogenesis of parathyroid carcinomas. While decreased expression of these genes might contribute to parathyroid carcinomatosis in a secondary fashion and 13q loss warrants further study as a diagnostic marker for parathyroid carcinoma, the putative 13q tumour suppressor awaits identification.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias das Paratireoides
/
Cromossomos Humanos Par 13
/
Carcinoma
/
Genes do Retinoblastoma
/
Genes Supressores de Tumor
/
Genes BRCA2
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article