title: Mutational analyses of RB and BRCA2 as candidate tumour suppressor genes in parathyroid carcinoma.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Molecular Medicine and Division of Endocrinology & Metabolism, University of Connecticut School of Medicine, Farmington, 06030-3101, USA.
authors.forename: Trisha M
authors.initials: TM
authors.lastname: Shattuck
authors.forename: Teresa S
authors.initials: TS
authors.lastname: Kim
authors.forename: Jessica
authors.initials: J
authors.lastname: Costa
authors.forename: David W
authors.initials: DW
authors.lastname: Yandell
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Imanishi
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.forename: Randall D
authors.initials: RD
authors.lastname: Gaz
authors.forename: Dolores
authors.initials: D
authors.lastname: Shoback
authors.forename: Orlo H
authors.initials: OH
authors.lastname: Clark
authors.forename: John M
authors.initials: JM
authors.lastname: Monchik
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Wierman
authors.forename: Anthony
authors.initials: A
authors.lastname: Hollenberg
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tojo
authors.forename: R S K
authors.initials: RS
authors.lastname: Chaganti
authors.forename: Andrew
authors.initials: A
authors.lastname: Arnold
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D024522:Genes, BRCA2; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D009693:Nucleic Acid Hybridization / Q000379:methods; D010282:Parathyroid Neoplasms / Q000235:genetics*
chemical_list: D017931:DNA Primers