|
Sign In to gain access to subscriptions and/or personal tools.
|
PTCH Gene Mutations in Odontogenic Keratocysts
D.C. Barreto
Departments of Clinics, Pathology and Surgery
R.S. Gomez
Departments of Clinics, Pathology and Surgery
A.E. Bale
Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA
W.L. Boson
Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
L. De Marco
Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
An odontogenic keratocyst (OKC) is a benign cystic lesion of the jaws that occurs sporadically or in association with nevoid basal cell carcinoma syndrome (NBCCS). Recently, the gene for NBCCS was cloned and shown to be the human homologue of the Drosophila segment polarity gene Patched (PTCH), a tumor suppressor gene. The PTCH gene encodes a transmembrane protein that acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues, including tooth. We investigated three cases of sporadic odontogenic keratocysts and three other cases associated with NBCCS, looking for mutations of the PTCH gene. Non-radioactive single-strand conformational polymorphism and direct sequencing of PCR products revealed a deletion of 5 base pairs (bp) in exon 3 (518delAAGCG) in one sporadic cyst as well as mutations in two cysts associated with NBCCS, a nonsense (C2760A) and a missense (G3499A) alteration. This report is the first to describe a somatic mutation of PTCH in sporadic odontogenic keratocysts as well as two novel mutations in cysts associated with NBCCS, indicating a similar pathogenesis in a subset of sporadic keratocysts.
Key Words: PTCH • mutation • keratocyst.
REFERENCES
- Alcedo J., Noll M. ( 1997). Hedgehog and its patched-smoothened receptor complex: a novel signalling mechanism at the cell surface. Biol Chem 378:583-590.[Medline]
[Order article via Infotrieve]
- Bale AE ( 1997). The nevoid basal cell carcinoma syndrome: genetics and mechanism of carcinogenesis. Cancer Invest 15:180-186.[Medline]
[Order article via Infotrieve]
- Boom R., Sol CJ, Salimans MM, Jansen CL, Wertheim-van Dillen PM, van der Noordaa J. (1990). Rapid and simple method for purification of nucleic acids. J Clin Microbiol 28:495-503.[Abstract/Free Full Text]
- Chenevix-Trench G., Wicking C., Berckman J., Sharpe H., Hockey A., Haan E., et al. (1993). Further localization of the gene for nevoid basal cell carcinoma syndrome (NBCCS) in 15 Australasian families: linkage and loss of heterozygosity. Am J Hum Genet 53:760-767.[Medline]
[Order article via Infotrieve]
- Farndon PA, Del Mastro RG, Evans DG, Kilpatrick MW (1992). Location of gene for Gorlin syndrome. Lancet 339:581-582.[CrossRef][Medline]
[Order article via Infotrieve]
- 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.[CrossRef][Medline]
[Order article via Infotrieve]
- Goodrich LV, Johnson RL, Milenkovic L., McMahon JA, Scott MP (1996). Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog. Genes Dev 10:301-312.[Abstract/Free Full Text]
- Gorlin RJ (1987). Nevoid basal cell carcinoma syndrome. Medicine 16:98-113.
- 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.[CrossRef][Medline]
[Order article via Infotrieve]
- Hardcastle Z., Mo R., Hui CC, Sharpe PT (1998). The Shh signalling pathway in tooth development: defects in Gli2 and Gli3 mutants. Development 125:2803-2811.[Abstract]
- Hooper JE, Scott MP (1989). The Drosophila patched gene encodes a putative membrane protein required for segmental patterning. Cell 59:751-765.[CrossRef][Medline]
[Order article via Infotrieve]
- Ingham PW, Taylor AM, Nakano Y. (1991). Role of the Drosophila patched gene in positional signalling. Nature 353:184-187.[CrossRef][Medline]
[Order article via Infotrieve]
- 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.[Abstract]
- Knudson AG Jr (1971). Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820-823.[Abstract/Free Full Text]
- Lench NJ, High AS, Markham AF, Hume WJ, Robinson PA (1996). Investigation of chromosome 9q22.3-q31 DNA marker loss in odontogenic keratocysts. Eur J Cancer B Oral Oncol 32(B):202-206.[CrossRef]
- 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.[CrossRef][Medline]
[Order article via Infotrieve]
- 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.[CrossRef][Medline]
[Order article via Infotrieve]
- Pietsch T., Waha A., Koch A., Kraus J., Albrecht S., Tonn J., et al. (1997). Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res 57:2085-2088.[Abstract/Free Full Text]
- Qian F., Watnick TJ, Onuchic LF, Germino GG (1996). The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type 1. Cell 87:979-987.[CrossRef][Medline]
[Order article via Infotrieve]
- Raffel C., Jenkins RB, Frederick L., Hebrink D., Alderete B., Fults DW, et al. (1997). Sporadic medulloblastomas contain PTCH mutations. Cancer Res 57:842-845.[Abstract/Free Full Text]
- Reis A., Kuster W., Linss G., Gebel E., Hamm H., Fuhrmann W., et al. (1992). Localisation of gene for naevoid basal cell carcinoma syndrome. Lancet 339:617.[CrossRef][Medline]
[Order article via Infotrieve]
- Sidransky D. (1996). Is human patched the gatekeeper of common skin cancers? Nat Genet 14:7-8.[CrossRef][Medline]
[Order article via Infotrieve]
- 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.[Abstract/Free Full Text]
- Wicking C., Shanley S., Smyth I., Gillies S., Negus K., Graham S., et al. (1997). Most germ-line mutations in the nevoid basal cell carcinoma syndrome lead to a premature termination of the PATCHED protein, and no genotype-phenotype correlations are evident. Am J Hum Genet 60:21-26.[Medline]
[Order article via Infotrieve]
- Wolter M., Reifenberger J., Sommer C., Ruzicka T., Reifenberger G. (1997). Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res 57:2581-2585.[Abstract/Free Full Text]
- Woolgar JA, Rippin JW, Browne RM (1987). The odontogenic keratocyst and its occurrence in the nevoid basal cell carcinoma syndrome. Oral Surg Oral Med Oral Pathol 64:727-730.[Medline]
[Order article via Infotrieve]
- 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.[Abstract/Free Full Text]
- Yap Eph, McGee O'D (1994). Non-isotopic single-strand conformation polymorphism (SSCP) analysis of PCR products. In: PCR technology: current innovation. Griffin HG, Griffin AM, editors. Boca Raton, FL: CRC Press, pp. 165-177.
Journal of Dental Research, Vol. 79, No. 6,
1418-1422 (2000)
DOI: 10.1177/00220345000790061101
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
Y. Gao, G. Yang, T. Weng, J. Du, X. Wang, J. Zhou, S. Wang, and X. Yang
Disruption of Smad4 in Odontoblasts Causes Multiple Keratocystic Odontogenic Tumors and Tooth Malformation in Mice
Mol. Cell. Biol.,
November 1, 2009;
29(21):
5941 - 5951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Lam, L Lee, S. Perschbacher, and M. Pharoah
The occurrence of keratocystic odontogenic tumours in nevoid basal cell carcinoma syndrome
Dentomaxillofac. Radiol.,
October 1, 2009;
38(7):
475 - 479.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L.-S. Sun, X.-F. Li, and T.-J. Li
PTCH1 and SMO Gene Alterations in Keratocystic Odontogenic Tumors
Journal of Dental Research,
June 1, 2008;
87(6):
575 - 579.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Grachtchouk, J. Liu, A. Wang, L. Wei, C. K. Bichakjian, J. Garlick, A. F. Paulino, T. Giordano, and A. A. Dlugosz
Odontogenic Keratocysts Arise from Quiescent Epithelial Rests and Are Associated with Deregulated Hedgehog Signaling in Mice and Humans
Am. J. Pathol.,
September 1, 2006;
169(3):
806 - 814.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Hu, J. M. Bonifas, G. Aragon, L. Kopelovich, Y. Liang, S. Ohta, M. A. Israel, D. R. Bickers, M. Aszterbaum, and E. H. Epstein Jr.
Evidence for Lack of Enhanced Hedgehog Target Gene Expression in Common Extracutaneous Tumors
Cancer Res.,
March 1, 2003;
63(5):
923 - 928.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
