RAD51 as a candidate parathyroid tumour suppressor gene on chromosome 15q: absence of somatic mutations.
OBJECTIVE
Loss of heterozygosity (LOH) at chromosome 15q is frequent in parathyroid adenomas, but no tumour suppressor gene of importance to parathyroid tumour development has been isolated from this region. The RAD51 gene has been localized to chromosome 15q and possesses regulatory functions involving DNA stability and cell proliferation, suggesting its possible role in tumorigenesis. Additionally, mutations in the RAD51 gene cause reduced resistance to ionizing radiation, which is a major risk factor for primary hyperparathyroidism. RAD51 was therefore analysed as a candidate tumour suppressor gene in a group of parathyroid adenomas for which mutations in a 15q tumour suppressor should be most readily detectable.


METHODS
From a total of 55 parathyroid adenomas, nine were selected based on their LOH pattern showing DNA loss at chromosome 15q in the vicinity of the RAD51 gene. RAD51 mRNA expression was investigated by reverse transcription-polymerase chain reaction (RT-PCR), and sequence analysis of the entire coding region of the RAD51 cDNA was performed in all nine adenomas.


RESULTS
RAD51 mRNA expression was substantiated in all parathyroid adenomas. Compared with the normal RAD51 cDNA sequence, no point mutations or microdeletions could be found in the parathyroid tumor cDNA.


CONCLUSIONS
These observations suggest that somatic inactivating mutations of the RAD51 gene are uncommonly, if ever, associated with parathyroid tumourigenesis.
Carling
T
T
Center of Molecular Medicine and Division of Endocrinology & Metabolism, University of Connecticut School of Medicine, Farmington, CT 06030-3101, USA.
Imanishi
Y
Y
Gaz
R D
RD
Arnold
A
A
D000236:Adenoma / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D010282:Parathyroid Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051135:Rad51 Recombinase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C495153:RAD51 protein, human; D051135:Rad51 Recombinase