Sage Journals: Discover world-class research

Abstract

Odontogenic keratocysts are relatively common lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (or Gorlin syndrome). The PTCH gene has been reported to be associated with Gorlin syndrome. We investigated 10 cases of non-syndromic keratocysts and two other cases associated with Gorlin syndrome, looking for PTCH mutations. Four novel and 1 known PTCH mutations were identified in five individual patients. Of the 5 mutations identified, 2 were germ-line mutations (2619C>A; 1338_1339insGCG) in 2 cysts associated with Gorlin syndrome, and 3 were somatic mutations (3124_3129dupGTGTGC; 1361_1364delGTCT; 3913G>T) in 3 non-syndromic cysts. This report describes PTCH mutations in both non-syndromic and Gorlin-syndrome-related odontogenic keratocysts in Chinese patients, and suggests that defects of PTCH are associated with the pathogenesis of syndromic as well as a subset of non-syndromic keratocysts.

Get full access to this article

View all access options for this article.

References

Barreto DC, Gomez RS, Bale AE, Boson WL, De Marco L (2000). PTCH gene mutations in odontogenic keratocysts. J Dent Res 79:1418–1422.

Bodak N, Queille S, Avril MF, Bouadjar B, Drougard C, Sarasin A, et al. (1999). High levels of patched gene mutations in basal-cell carcinomas from patients with xeroderma pigmentosum. Proc Natl Acad Sci USA 96:5117–5122.

Boutet N, Bignon YJ, Drouin-Garraud V, Sarda P, Longy M, Lacombe D, et al. (2003). Spectrum of PTCH1 mutations in French patients with Gorlin syndrome. J Invest Dermatol 121:478–481.

Browne RM (1971). The odontogenic keratocyst. Histological features and their correlation with clinical behaviour. Br Dent J 131:249–259.

Chidambaram A, Goldstein AM, Gailani MR, Gerrard B, Bal SJ, DiGiovanna JJ, et al. (1996). Mutations in the human homologue of the Drosophila patched gene in Caucasian and African-American nevoid basal cell carcinoma syndrome patients. Cancer Res 56:4599–4601.

Cobourne MT, Miletich I, Sharpe PT (2004). Restriction of sonic hedgehog signalling during early tooth development. Development 131:2875–2885.

Dassule HR, Lewis P, Bei M, Maas R, McMahon AP (2000). Sonic hedgehog regulates growth and morphogenesis of the tooth. Development 127:4775–4785.

den Dunnen JT, Antonarakis SE (2000). Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 15:7–12.

Evans DG, Farndon PA (2004). Nevoid basal cell carcinoma syndrome. Gene Review, at www.genetests.org.

10.

Fujii K, Kohno Y, Sugita K, Nakamura M, Moroi Y, Urabe K, et al. (2003). Mutations in the human homologue of Drosophila patched in Japanese nevoid basal cell carcinoma syndrome patients. Hum Mutat 21:451–452.

11.

Gailani MR, Stahle-Backdahl M, Leffell DJ, Glynn M, Zaphiropoulos PG, Pressman C, et al. (1996). The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Genet 14:78–81.

12.

Gorlin RJ (1987). Nevoid basal-cell carcinoma syndrome. Medicine (Baltimore) 66:98–113.

13.

Hahn H, Wicking C, Zaphiropoulos PG, Gailani MR, Shanley S, Chidambaram A, et al. (1996). Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85:841–851.

14.

Hardcastle Z, Mo R, Hui CC, Sharpe PT (1998). The Shh signaling pathway in tooth development: defects in Gli2 and Gli3 mutants. Development 125:2803–2811.

15.

Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, et al. (1996). Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272:1668–1671.

16.

Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, et al. (1997). Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 69:299–308.

17.

Lench NJ, Telford EA, High AS, Markham AF, Wicking C, Wainwright BJ (1997). Characterisation of human patched germ line mutations in naevoid basal cell carcinoma syndrome. Hum Genet 100:497–502.

18.

Levanat S, Gorlin RJ, Fallet S, Johnson DR, Fantasia JE, Bale AE (1996). A two-hit model for developmental defects in Gorlin syndrome. Nat Genet 12:85–87.

19.

Li TJ, Browne RM, Matthews JB (1994). Quantification of PCNA+ cells within odontogenic jaw cyst epithelium. J Oral Pathol Med 23:184–189.

20.

Lo Muzio L, Nocini PF, Savoia A, Consolo U, Procaccini M, Zelante L, et al (1999a). Nevoid basal cell carcinoma syndrome. Clinical findings in 37 Italian affected individuals. Clin Genet 55:34–40.

21.

Lo Muzio L, Nocini P, Bucci P, Pannone G, Consolo U, Procaccini M (1999b). Early diagnosis of nevoid basal cell carcinoma syndrome. J Am Dent Assoc 130:669–674.

22.

Ohki K, Kumamoto H, Ichinohasama R, Sato T, Takahashi N, Ooya K (2004). PTC gene mutations and expression of SHH, PTC, SMO, and GLI-1 in odontogenic keratocysts. Int J Oral Maxillofac Surg 33:584–592.

23.

Richards FM, Goudie DR, Cooper WN, Jene Q, Barroso I, Wicking C, et al. (1997). Mapping the multiple self-healing squamous epithelioma (MSSE) gene and investigation of xeroderma pigmentosum group A (XPA) and PATCHED (PTCH) as candidate genes. Hum Genet 101:317–322.

24.

Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, et al. (1996). The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature 384:129–134.

25.

Strange RC, El-Genidy N, Ramachandran S, Lovatt TJ, Fryer AA, Smith AG, et al. (2004). Susceptibility to basal cell carcinoma: associations with PTCH polymorphisms. Ann Hum Genet 68(Pt 6):536–545.

26.

Strutt H, Thomas C, Nakano Y, Stark D, Neave B, Taylor AM, et al. (2001). Mutations in the sterol-sensing domain of Patched suggest a role for vesicular trafficking in Smoothened regulation. Curr Biol 11:608–613.

27.

Vorechovsky I, Unden AB, Sandstedt B, Toftgard R, Stahle-Backdahl M (1997). Trichoepitheliomas contain somatic mutations in the overexpressed PTCH gene: support for a gatekeeper mechanism in skin tumorigenesis. Cancer Res 57:4677–4681.

28.

Xie J, Johnson RL, Zhang X, Bare JW, Waldman FM, Cogen PH, et al. (1997). Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors. Cancer Res 57:2369–2372.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.47 MB

PTCH Mutations in Sporadic and Gorlin-syndrome-related Odontogenic Keratocysts

Abstract

Get full access to this article

References

Supplementary Material