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Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation.
Endocr Relat Cancer. 2007 Jun; 14(2):493-9.ER

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.

Authors+Show Affiliations

Department of Endocrinology and Metabolism, University of Pise, Pise, Italy. cetani@endoc.med.unipi.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17639062

Citation

Cetani, F, et al. "Different Somatic Alterations of the HRPT2 Gene in a Patient With Recurrent Sporadic Primary Hyperparathyroidism Carrying an HRPT2 Germline Mutation." Endocrine-related Cancer, vol. 14, no. 2, 2007, pp. 493-9.
Cetani F, Pardi E, Ambrogini E, et al. Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation. Endocr Relat Cancer. 2007;14(2):493-9.
Cetani, F., Pardi, E., Ambrogini, E., Viacava, P., Borsari, S., Lemmi, M., Cianferotti, L., Miccoli, P., Pinchera, A., Arnold, A., & Marcocci, C. (2007). Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation. Endocrine-related Cancer, 14(2), 493-9.
Cetani F, et al. Different Somatic Alterations of the HRPT2 Gene in a Patient With Recurrent Sporadic Primary Hyperparathyroidism Carrying an HRPT2 Germline Mutation. Endocr Relat Cancer. 2007;14(2):493-9. PubMed PMID: 17639062.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation. AU - Cetani,F, AU - Pardi,E, AU - Ambrogini,E, AU - Viacava,P, AU - Borsari,S, AU - Lemmi,M, AU - Cianferotti,L, AU - Miccoli,P, AU - Pinchera,A, AU - Arnold,A, AU - Marcocci,C, PY - 2007/7/20/pubmed PY - 2007/12/6/medline PY - 2007/7/20/entrez SP - 493 EP - 9 JF - Endocrine-related cancer JO - Endocr Relat Cancer VL - 14 IS - 2 N2 - 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. SN - 1351-0088 UR - https://www.unboundmedicine.com/medline/citation/17639062/Different_somatic_alterations_of_the_HRPT2_gene_in_a_patient_with_recurrent_sporadic_primary_hyperparathyroidism_carrying_an_HRPT2_germline_mutation_ L2 - https://erc.bioscientifica.com/doi/10.1677/ERC-06-0092 DB - PRIME DP - Unbound Medicine ER -