This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cetani, F. Articles by Marcocci, C. Search for Related Content PubMed PubMed Citation Articles by Cetani, F. Articles by Marcocci, C.

Genetic Analyses of the HRPT2 Gene in Primary Hyperparathyroidism: Germline and Somatic Mutations in Familial and Sporadic Parathyroid Tumors

Departments of Endocrinology and Metabolism (F.C., E.P., S.B., G.D., L.C., E.A., A.P., C.M.), Oncology, Section of Pathology (P.V.), and Surgery (P.B., P.M.), University of Pisa, 56124 Pisa, Italy; Endocrine and Metabolic Sciences, University of Genoa (E.G.), 16132 Genoa, Italy; and Nephrology Unit, Circolo Hospital and Macchi Foundation (G.C.), 21100 Varese, Italy

Address all correspondence and requests for reprints to: Dr. Filomena Cetani, Dipartimento di Endocrinologia e Metabolismo, Università di Pisa, Via Paradisa 2, 56124 Pisa, Italy. E-mail: cetani{at}endoc.med.unipi.it.

We investigated the involvement of the HRPT2 gene by loss of heterozygosity analysis and direct sequencing in a kindred with hyperparathyroidism-jaw tumor syndrome (HPT-JT) and three kindreds with familial isolated primary hyperparathyroidism (FIHP). Seven patients with sporadic parathyroid cancers and 35 with parathyroid adenomas with no family history of primary hyperparathyroidism or HPT-JT were also studied. A germline heterozygous substitution G to A was found in the donor splice site of intron 1 in one of the three FIHP families. No mutations were identified in the HPT-JT kindred. A somatic HRPT2 mutation was found in four of seven patients with parathyroid cancers, two of which were unreported frameshift mutations (195insT and 195insA) in exon 2. Consistent with recent findings, two of seven patients with sporadic parathyroid cancer had germline mutations. Four adenomas showed loss of heterozygosity at HRPT2, whereas a somatic HRPT2 mutation was found in one. In conclusion, we provide additional evidence for a strong association between HRPT2 gene mutations and sporadic parathyroid cancer. The finding that two of the seven patients with sporadic parathyroid cancer carried an HRPT2 germline mutation suggests that they might have occult HPT-JT. Our results also confirm the need for testing HRPT2 gene in FIHP families.

This article has been cited by other articles:

				M. A Hahn, J. McDonnell, and D. J Marsh The effect of disease-associated HRPT2 mutations on splicing J. Endocrinol., June 1, 2009; 201(3): 387 - 396. [Abstract] [Full Text] [PDF]

				V. M. Howell, A. Gill, A. Clarkson, A. E. Nelson, R. Dunne, L. W. Delbridge, B. G. Robinson, B. T. Teh, O. Gimm, and D. J. Marsh Accuracy of Combined Protein Gene Product 9.5 and Parafibromin Markers for Immunohistochemical Diagnosis of Parathyroid Carcinoma J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 434 - 441. [Abstract] [Full Text] [PDF]

				G. Masi, L. Barzon, M. Iacobone, G. Viel, A. Porzionato, V. Macchi, R. De Caro, G. Favia, and G. Palu Clinical, genetic, and histopathologic investigation of CDC73-related familial hyperparathyroidism Endocr. Relat. Cancer, December 1, 2008; 15(4): 1115 - 1126. [Abstract] [Full Text] [PDF]

				L. Lin, J.-H. Zhang, L. M. Panicker, and W. F. Simonds The parafibromin tumor suppressor protein inhibits cell proliferation by repression of the c-myc proto-oncogene PNAS, November 11, 2008; 105(45): 17420 - 17425. [Abstract] [Full Text] [PDF]

				F Cetani, E Pardi, E Ambrogini, P Viacava, S Borsari, M Lemmi, L Cianferotti, P Miccoli, A Pinchera, A Arnold, 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, June 1, 2007; 14(2): 493 - 499. [Abstract] [Full Text] [PDF]

				C C Juhlin, A Villablanca, K Sandelin, F Haglund, J Nordenstrom, L Forsberg, R Branstrom, T Obara, A Arnold, C Larsson, et al. Parafibromin immunoreactivity: its use as an additional diagnostic marker for parathyroid tumor classification Endocr. Relat. Cancer, June 1, 2007; 14(2): 501 - 512. [Abstract] [Full Text] [PDF]

				F. Cetani, E. Ambrogini, P. Viacava, E. Pardi, G. Fanelli, A. G. Naccarato, S. Borsari, M. Lemmi, P. Berti, P. Miccoli, et al. Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma? Eur. J. Endocrinol., May 1, 2007; 156(5): 547 - 554. [Abstract] [Full Text] [PDF]

				L. Lin, M. Czapiga, L. Nini, J.-H. Zhang, and W. F. Simonds Nuclear Localization of the Parafibromin Tumor Suppressor Protein Implicated in the Hyperparathyroidism-Jaw Tumor Syndrome Enhances Its Proapoptotic Function Mol. Cancer Res., February 1, 2007; 5(2): 183 - 193. [Abstract] [Full Text] [PDF]

				V. M. Howell, J. W. Cardinal, A.-L. Richardson, O. Gimm, B. G. Robinson, and D. J. Marsh Rapid Mutation Screening for HRPT2 and MEN1 Mutations Associated with Familial and Sporadic Primary Hyperparathyroidism J. Mol. Diagn., November 1, 2006; 8(5): 559 - 566. [Abstract] [Full Text] [PDF]

				S. J. Marx and W. F. Simonds Imaging to detect early endocrine cancers. J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2861 - 2863. [Full Text] [PDF]

				V. Guarnieri, A. Scillitani, L. A. Muscarella, C. Battista, N. Bonfitto, M. Bisceglia, S. Minisola, M. L. Mascia, L. D'Agruma, and D. E. C. Cole Diagnosis of Parathyroid Tumors in Familial Isolated Hyperparathyroidism with HRPT2 Mutation: Implications for Cancer Surveillance J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2827 - 2832. [Abstract] [Full Text] [PDF]

				M. R. Rubin and S. J. Silverberg HRPT2 in Parathyroid Cancer: A Piece of the Puzzle J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5505 - 5507. [Full Text] [PDF]

				L. J. Krebs, T. M. Shattuck, and A. Arnold HRPT2 Mutational Analysis of Typical Sporadic Parathyroid Adenomas J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5015 - 5017. [Abstract] [Full Text] [PDF]

				K J Bradley, B M Cavaco, M R Bowl, B Harding, A Young, and R V Thakker Utilisation of a cryptic non-canonical donor splice site of the gene encoding PARAFIBROMIN is associated with familial isolated primary hyperparathyroidism J. Med. Genet., August 1, 2005; 42(8): e51 - e51. [Abstract] [Full Text] [PDF]