Abstract
Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a familial multi-tumor syndrome resulting from inactivating mutations in the HRPT2 tumor suppressor gene, which encodes a protein product named parafibromin. Here, we will review recent advances in genetic and protein studies on parafibromin, and examine its biological functions.
Key words
Hyperparathyroidism-jaw tumor syndrome - HRPT2 - Parafibromin - Parathyroid carcinoma
References
-
1
Jackson C E, Norum R A, Boyd S B, Talpos G B, Wilson S D, Taggart R T, Mallette L E.
Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome.
Surgery.
1990;
108
1006-1012; discussion 1012 - 1013
-
2
Carpten J D, Robbins C M, Villablanca A, Forsberg L, Presciuttini S, Bailey-Wilson J, Simonds W F, Gillanders E M, Kennedy A M, Chen J D, Agarwal S K, Sood R, Jones M P, Moses T Y, Haven C, Petillo D, Leotlela P D, Harding B, Cameron D, Pannett A A, Hoog A, Heath H 3rd, James-Newton L A, Robinson B, Zarbo R J, Cavaco B M, Wassif W, Perrier N D, Rosen I B, Kristoffersson U, Turnpenny P D, Farnebo L O, Besser G M, Jackson C E, Morreau H, Trent J M, Thakker R V, Marx S J, Teh B T, Larsson C, Hobbs M R.
HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome.
Nat Genet.
2002;
32
676-680
-
3
Cavaco B M, Guerra L, Bradley K J, Carvalho D, Harding B, Oliveira A, Santos M A, Sobrinho L G, Thakker R V, Leite V J.
Hyperparathyroidism-jaw tumor syndrome in Roma families from Portugal is due to a founder mutation of the HRPT2 gene.
J Clin Endocrinol Metab.
2004;
89
1747-1752
-
4
Chen J D, Morrison C, Zhang C, Kahnoski K, Carpten J D, Teh B T.
Hyperparathyroidism-jaw tumour syndrome.
J Intern Med.
2003;
253
634-642
-
5
Bradley K J, Hobbs M R, Buley I D, Carpten J D, Cavaco B M, Fares J E, Laidler P, Manek S, Robbins C M, Salti I S, Thompson N W, Jackson C E, Thakker R V.
Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome.
J Intern Med.
2005;
257
18-26
-
6
Szabo J, Heath B, Hill V M, Jackson C E, Zarbo R J, Mallette L E, Chew S L, Besser G M, Thakker R V, Huff V. et al .
Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2 maps to chromosome 1q21-q31.
Am J Hum Genet.
1995;
56
944-950
-
7
Teh B T, Farnebo F, Kristoffersson U, Sundelin B, Cardinal J, Axelson R, Yap A, Epstein M, Heath H 3rd, Cameron D, Larsson C.
Autosomal dominant primary hyperparathyroidism and jaw tumor syndrome associated with renal hamartomas and cystic kidney disease: linkage to 1q21-q32 and loss of the wild type allele in renal hamartomas.
J Clin Endocrinol Metab.
1996;
81
4204-4211
-
8
Teh B T, Farnebo F, Twigg S, Hoog A, Kytola S, Korpi-Hyovalti E, Wong F K, Nordenstrom J, Grimelius L, Sandelin K, Robinson B, Farnebo L O, Larsson C.
Familial isolated hyperparathyroidism maps to the hyperparathyroidism-jaw tumor locus in 1q21-q32 in a subset of families.
J Clin Endocrinol Metab.
1998;
83
2114-2120
-
9
Cavaco B M, Barros L, Pannett A A, Ruas L, Carvalheiro M, Ruas M M, Krausz T, Santos M A, Sobrinho L G, Leite V, Thakker R V.
The hyperparathyroidism-jaw tumour syndrome in a Portuguese kindred.
QJM.
2001;
94
213-222
-
10
Howell V M, Haven C J, Kahnoski K, Khoo S K, Petillo D, Chen J, Fleuren G J, Robinson B G, Delbridge L W, Philips J, Nelson A E, Krause U, Hammje K, Dralle H, Hoang-Vu C, Gimm O, Marsh D J, Morreau H, Teh B T.
HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours.
J Med Genet.
2003;
40
657-663
-
11
Shattuck T M, Valimaki S, Obara T, Gaz R D, Clark O H, Shoback D, Wierman M E, Tojo K, Robbins C M, Carpten J D, Farnebo L O, Larsson C, Arnold A.
Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma.
N Engl J Med.
2003;
349 (18)
1722-1729
-
12
Cavaco B M, Guerra L, Bradley K J, Cavalho D, Harding B, Oliveira A, Santos M A, Sobrinho L G, Thakker R V, Leite V.
Hyperparathyroidism-jaw tumor syndrome in Roma families from Portugal is due to a founder mutation of the HRPT2 gene.
J Clin Endocrinol Metab.
2004;
89
1747-1752
-
13
Cetani F, Pardi E, Borsari S, Viacava P, Dipollina G, Cianferotti L, Ambrogini E, Gazzerro E, Colussi G, Berti P, Miccoli P, Pinchera A, Marcocci C.
Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors.
J Clin Endocrinol Metab.
2004;
89
5583-5591
-
14
Moon S D, Park J H, Kim E M, Kim J H, Han J H, Yoo S J, Yoon K H, Kang M I, Lee K W, Son H Y, Kang S K, Oh S J, Kim K M, Yoon S J, Park J G, Kim I J, Kang H C, Hong S W, Kim K R, Cha B Y.
A Novel IVS2 - 1G > A Mutation Causes Aberrant Splicing of the HRPT2 Gene in a Family with Hyperparathyroidism-Jaw Tumor Syndrome.
J Clin Endocrinol Metab.
2005;
90
878-883
-
15
Haven C J, Howell V M, Eilers P H, Dunne R, Takahashi M, van Puijenbroek M, Furge K, Kievit J, Tan M H, Fleuren G J, Robinson B G, Delbridge L W, Philips J, Nelson A E, Krause U, Dralle H, Hoang-Vu C, Gimm O, Horreau H, Marsh D J, Teh B T.
Gene expression of parathyroid tumors: molecular subclassification and identification of the potential malignant phenotype.
Cancer Res.
2004;
64
7405-7411
-
16
Tan M H, Morrison C, Wang P, Yang X, Haven C J, Zhang C, Zhao P, Tretiakova M S, Korpi-Hyovalti E, Burgess J R, Soo K C, Cheah W K, Cao B, Resau J, Morreau H, Teh B T.
Loss of parafibromin immunoreactivity is a distinguishing feature of parathyroid carcinoma.
Clin Cancer Res.
2004;
10
6629-6637
-
17
Woodard G E, Lin L, Zhang J H, Agarwal S K, Marx S J, Simonds W F.
Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression.
Oncogene.
2005;
24
1272-1276
-
18
Tan M H, Teh B T.
Renal neoplasia in the hyperparathyroidism-jaw tumor syndrome.
Curr Mol Med.
2004;
4
895-897
-
19
Rozenblatt-Rosen O, Hughes C M, Nannepaga S J, Shanmugam K S, Copeland T D, Guszczynski T, Resau J H, Meyerson M.
The parafibromin tumor suppressor protein is part of a human Paf1 complex.
Mol Cell Biol.
2005;
25
612-620
-
20
Chang M, French-Cornay D, Fan H Y, Klein H, Denis C L, Jaehning J A.
A complex containing RNA polymerase II, Paf1p, Cdc73p, Hpr1p, and Ccr4p plays a role in protein kinase C signaling.
Mol Cell Biol.
1999;
19
1056-1067
-
21
Krogan N J, Kim M, Ahn S H, Zhong G, Kobor M S, Cagney G, Emili A, Shilatifard A, Buratowski S, Greenblatt J F.
RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach.
Mol Cell Biol.
2002;
22
6979-6992
-
22
Wood A, Schneider J, Dover J, Johnston M, Shilatifard A.
The Paf1 complex is essential for histone monoubiquitination by the Rad6-Bre1 complex, which signals for histone methylation by COMPASS and Dot1p.
J Biol Chem..
2003;
278
34739-34742
-
23
Hughes C M, Rozenblatt-Rosen O, Milne T A, Copeland T D, Levine S S, Lee J C, Hayes D N, Shanmugam K S, Bhattacharjee A, Biondi C A, Kay G F, Hayward N K, Hess J L, Meyerson M.
Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus.
Mol Cell.
2004;
13
587-597
-
24
Milne T A, Hughes C M, Lloyd R, Yang Z, Rozenblatt-Rosen O, Dou Y, Schnepp R W, Krankel C, Livolsi V A, Gibbs D, Hua X, Roeder R G, Meyerson M, Hess J L.
Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors.
Proc Natl Acad Sci.
2005;
102
749-754
-
25
Arnold A, Shattuck T M, Mallya S M, Krebs L J, Costa J, Gallagher J, Wild Y, Saucier K.
Molecular pathogenesis of primary hyperparathyroidism.
J Bone Miner Res.
2002;
17 Suppl 2
N30-N36
B. T. Teh, M. D., Ph. D.
Van Andel Research Institute
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