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Analysis of the RAD54 gene on chromosome 1p as a potential tumor‐suppressor gene in parathyroid adenomas
Author(s) -
Carling Tobias,
Imanishi Yasuo,
Gaz Randall D.,
Arnold Andrew
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990924)83:1<80::aid-ijc15>3.0.co;2-e
Subject(s) - loss of heterozygosity , biology , tumor suppressor gene , carcinogenesis , cancer research , point mutation , germline mutation , exon , genetics , mutation , gene , allele , microbiology and biotechnology
Parathyroid adenomas causing primary hyperparathyroidism (pHPT) frequently exhibit allelic loss of DNA markers on the short arm of chromosome 1, indicating the presence of one or more tumor‐suppressor genes on 1p. Since the development of pHPT is enhanced in individuals exposed to ionizing radiation to the neck, it could be anticipated that genes involved in DNA repair and recombination may be special targets for mutation in parathyroid tumorigenesis, whether irradiation‐associated or not. RAD54 is a member of a family of genes involved in such functions, and RAD54 knockout mice show increased sensitivity to ionizing radiation. The localization of the RAD54 gene to 1p32 has therefore elevated it to a most compelling candidate parathyroid tumor‐suppressor gene. Twelve parathyroid adenomas demonstrating allelic loss at chromosome 1p were selected from 55 parathyroid adenomas previously analyzed for loss of heterozygosity using polymorphic microsatellite markers. All 18 exons of the RAD54 gene were fully analyzed by automated sequencing for detection of point mutations or micro‐deletions in each parathyroid adenoma. No mutational aberrations were detected in the RAD54 gene, strongly suggesting that complete somatic inactivation of RAD54 is infrequently, if ever, associated with the development of parathyroid adenomas. Whether genes controlling DNA repair and recombination are involved in parathyroid neoplasia remains to be determined. Int. J. Cancer 83:80–82, 1999. © 1999 Wiley‐Liss, Inc.