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Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation
- Source :
- Endocrine-Related Cancer. 14:493-499
- Publication Year :
- 2007
- Publisher :
- Bioscientifica, 2007.
-
Abstract
- Early onset of primary hyperparathyroidism (PHPT) and multiglandular involvement suggest a familial form in which germline mutation of a PHPT-related gene(s) and a somatic event at the same locus can be often demonstrated. We investigated the involvement of multiple endocrine neoplasia type 1 (MEN1) and HRPT2 genes in a 39-year-old man with recurrent PHPT. PHPT was firstly diagnosed at the age of 21 and the patient had two recurrences separated by extended periods of normocalcemia. This unusual history prompted us to investigate other family members and study the MEN1 and HRPT2 genes. An HRPT2 germline missense mutation in exon 3 (R91P) was found in the index case, which was associated with different HRPT2 somatic alterations in each of the three examined parathyroid tumors. These findings are consistent with Knudson’s ‘two hit’ concept of biallelic inactivation of classical tumor suppressor genes. Screening of 15 asymptomatic relatives was negative for the R91P germline mutation. All the three abnormal parathyroid specimens showed cystic features at histology and were negative for parafibromin immunostaining. In one specimen, diffuse parafibromin staining was evident in a rim of normal parathyroid tissue surrounding the adenomatous lesion. Our study shows that different somatic genetic events at the HRPT2 locus are responsible for the asynchronous occurrence of multiple adenomas in a patient carrying an HRPT2 germline mutation. The finding of diffuse parafibromin staining in a rim of normal parathyroid tissue, but not in the contiguous adenomatous lesion, reinforces the concept that loss of parafibromin expression is responsible for the development of parathyroid tumors in this setting.
- Subjects :
- Adult
Male
Cancer Research
Somatic cell
Endocrinology, Diabetes and Metabolism
DNA Mutational Analysis
Parafibromin
Mutation, Missense
Loss of Heterozygosity
Biology
Germline
Parathyroid Glands
Endocrinology
Germline mutation
Recurrence
Proto-Oncogene Proteins
medicine
Humans
Missense mutation
MEN1
Multiple endocrine neoplasia
Germ-Line Mutation
Tumor Suppressor Proteins
Hyperparathyroidism, Primary
medicine.disease
Oncology
Cancer research
Primary hyperparathyroidism
Subjects
Details
- ISSN :
- 14796821 and 13510088
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Endocrine-Related Cancer
- Accession number :
- edsair.doi.dedup.....3a6608bc6427bc073fcf993559dbeb65