Absence of p53 point mutations in parathyroid adenoma and carcinoma.

Abstract

Primary hyperparathyroidism is a common disorder characterized by aberrant growth and function of solitary or multiple parathyroid glands. Many, if not all, parathyroid adenomas are examples of benign clonal neoplastic growth. The molecular events associated with the development of parathyroid neoplasia have not been well characterized. We examined benign and malignant parathyroid tissues for structural abnormalities of the p53 tumor suppressor gene. To screen for mutations in the p53 gene, we analyzed polymerase chain reaction-amplified DNA by denaturing gradient gel electrophoresis. DNA was isolated from 26 benign parathyroid adenomas and 3 parathyroid carcinomas, and polymerase chain reaction was used to amplify DNA fragments corresponding to the 4 evolutionarily conserved domains within exons 5, 7, and 8 of the p53 gene in which the majority of point mutations have been identified. Amplified DNA fragments were electrophoresed through polyacrylamide gels with linearly increasing gradients of the denaturants urea and formamide. After electrophoresis, the gels were examined for the presence of abnormally migrating bands, which represent DNA with altered melting points due to nucleotide sequence changes. Amplified fragments were of the expected size in DNA from 26 parathyroid adenomas and 3 parathyroid carcinomas. Denaturing gradient gel electrophoresis studies failed to disclose evidence of mutations in exons 5, 7, and 8 of the p53 gene in these neoplasms. We conclude that p53 point mutations do not appear to be a primary event responsible for neoplastic growth in parathyroid tissue.

Genomics and Epigenomics in Parathyroid Neoplasia: from Bench to Surgical Pathology Practice

“…TP53 gene mutations are among the most common genetic aberrations in malignant epithelial tumors, although these genetic events seem to be unusual in parathyroid carcinomas [103][104][105]. Even so, LOH of one TP53 allele seems to be more common [103].…”

Molecular genetic insights into sporadic primary hyperparathyroidism

“…As noted above, CCND1 gene amplification (Zhao et al 2014, Pandya et al 2017 and cyclin D1 overexpression (Vasef et al 1999, Zhao et al 2014 are frequently observed in parathyroid cancer. Several additional studies sought to interrogate candidate genes for sequence and/or expression abnormalities in parathyroid cancer, showing that such important human cancer genes as p53 (Cryns et al 1994b, Hakim & Levine 1994, RB1, BRCA2 (Shattuck et al 2003b), and others (Yoshimoto et al 1992, Cryns et al 1994a were unlikely to make a major contribution. The absence of alterations in such common 'cancer genes' was further confirmed by next-generation sequence analyses (Kasaian et al 2013, Yu et al 2015, Pandya et al 2017.…”

Clonal Analysis of Nodular Parathyroid Hyperplasia in Renal Hyperparathyroidism

“…As pathogenetic factors of parathyroid adenomas, the rearrangement and overexpression of the PRAD1/cyclin D1 gene, a cell cycle regulator, and loss of chromosome 11 DNA sequences usually including the postulated region of MEN-I gene have been noted [29 -31]. Inactivation of the retinoblastoma (RB) tumor suppressor gene, which normally inhibits progression through the cell cycle at the G 1 /S transition and P53 tumor suppressor gene abnormalities in parathyroid carcinoma, has been demonstrated [32][33][34].…”