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Science 14 June 1996:
Vol. 272. no. 5268, pp. 1668 - 1671
DOI: 10.1126/science.272.5268.1668
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Reports

Human Homolog of patched, a Candidate Gene for the Basal Cell Nevus Syndrome

Ronald L. Johnson, Alana L. Rothman, Jingwu Xie, Lisa V. Goodrich, John W. Bare, Jeannette M. Bonifas, Anthony G. Quinn, * Richard M. Myers, David R. Cox, Ervin H. Epstein Jr., dagger Matthew P. Scott dagger

The basal cell nevus syndrome (BCNS) is characterized by developmental abnormalities and by the postnatal occurrence of cancers, especially basal cell carcinomas (BCCs), the most common human cancer. Heritable mutations in BCNS patients and a somatic mutation in a sporadic BCC were identified in a human homolog of the Drosophila patched (ptc) gene. The ptc gene encodes a transmembrane protein that in Drosophila acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues. The human PTC gene appears to be crucial for proper embryonic development and for tumor suppression.

R. L. Johnson, L. V. Goodrich, M. P. Scott, Departments of Developmental Biology and Genetics, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305-5427, USA.
A. L. Rothman, J. Xie, J. W. Bare, J. M. Bonifas, A. G. Quinn, E. H. Epstein Jr., Department of Dermatology, San Francisco General Hospital, University of California, San Francisco, CA 94110, USA.
R. M. Myers and D. R. Cox, Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
* Present address: Department of Dermatology, St. Bartholomew's and the Royal Hospital School of Medicine, London, UK.
dagger To whom correspondence should be addressed.


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Cardiac and CNS defects in a mouse with targeted disruption of suppressor of fused.
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A. Vogt, P.-T. Chuang, J. Hebert, J. Hwang, Y. Lu, L. Kopelovich, M. Athar, D. R. Bickers, and E. H. Epstein Jr. (2004)
J. Exp. Med. 199, 753-761
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S. W. Altmann, H. R. Davis Jr., L.-j. Zhu, X. Yao, L. M. Hoos, G. Tetzloff, S. P. N. Iyer, M. Maguire, A. Golovko, M. Zeng, et al. (2004)
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The Kinesin-related Protein Costal2 Associates with Membranes in a Hedgehog-sensitive, Smoothened-independent Manner.
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J. Biol. Chem. 279, 7064-7071
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Basal Cell Carcinoma and Its Development: Insights from Radiation-Induced Tumors in Ptch1-Deficient Mice.
M. Mancuso, S. Pazzaglia, M. Tanori, H. Hahn, P. Merola, S. Rebessi, M. J. Atkinson, V. Di Majo, V. Covelli, and A. Saran (2004)
Cancer Res. 64, 934-941
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Abnormalities of the vitreoretinal interface caused by dysregulated Hedgehog signaling during retinal development.
G. C.M. Black, C. J. Mazerolle, Y. Wang, K. D. Campsall, D. Petrin, B. C. Leonard, K. F. Damji, D. G. Evans, D. McLeod, and V. A. Wallace (2003)
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A subset of familial colorectal neoplasia kindreds linked to chromosome 9q22.2-31.2.
G. L. Wiesner, D. Daley, S. Lewis, C. Ticknor, P. Platzer, J. Lutterbaugh, M. MacMillen, B. Baliner, J. Willis, R. C. Elston, et al. (2003)
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Loss of Protein Kinase C{alpha} Expression May Enhance the Tumorigenic Potential of Gli1 in Basal Cell Carcinoma.
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wingless signaling regulates the maintenance of ovarian somatic stem cells in Drosophila.
X. Song and T. Xie (2003)
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Emerging Roles for Hedgehog-Patched-Gli Signal Transduction in Reproduction.
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Yeast, Flies, Worms, and Fish in the Study of Human Disease.
I. K. Hariharan and D. A. Haber (2003)
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Transcriptional profiling of the Sonic hedgehog response: A critical role for N-myc in proliferation of neuronal precursors.
T. G. Oliver, L. L. Grasfeder, A. L. Carroll, C. Kaiser, C. L. Gillingham, S. M. Lin, R. Wickramasinghe, M. P. Scott, and R. J. Wechsler-Reya (2003)
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PNAS 100, 4616-4621
   Abstract »    Full Text »    PDF »
Several Human PATCHED1 Mutations Block Protein Maturation.
E. C. Bailey, L. Zhou, and R. L. Johnson (2003)
Cancer Res. 63, 1636-1638
   Abstract »    Full Text »    PDF »
GSK-3: tricks of the trade for a multi-tasking kinase.
B. W. Doble and J. R. Woodgett (2003)
J. Cell Sci. 116, 1175-1186
   Abstract »    Full Text »    PDF »
A positive role for Patched-Smoothened signaling in promoting cell proliferation during normal head development in Drosophila.
B. V. Shyamala and K. M. Bhat (2003)
Development 129, 1839-1847
   Abstract »    Full Text »    PDF »
Evidence for Lack of Enhanced Hedgehog Target Gene Expression in Common Extracutaneous Tumors.
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. (2003)
Cancer Res. 63, 923-928
   Abstract »    Full Text »    PDF »
A New Germline Mutation of the PTCH Gene in a Japanese Patient with Nevoid Basal Cell Carcinoma Syndrome Associated with Meningioma.
G. Tate, M. Li, T. Suzuki, and T. Mitsuya (2003)
Jpn. J. Clin. Oncol. 33, 47-50
   Abstract »    Full Text »    PDF »
Analysis of Gene Expression in the Normal and Malignant Cerebellum.
R. J. Wechsler-Reya (2003)
Recent Prog. Horm. Res. 58, 227-248
   Abstract »    Full Text »    PDF »
Genetic Disorders of Skin: A Decade of Progress.
A. S. Paller (2003)
Arch Dermatol 139, 74-77
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Null Mutation of DNA Strand Break-Binding Molecule Poly(ADP-ribose) Polymerase Causes Medulloblastomas in p53-/- Mice.
W.-M. Tong, H. Ohgaki, H. Huang, C. Granier, P. Kleihues, and Z.-Q. Wang (2003)
Am. J. Pathol. 162, 343-352
   Abstract »    Full Text »    PDF »
Significantly High Levels of Ultraviolet-specific Mutations in the Smoothened Gene in Basal Cell Carcinomas from DNA Repair-deficient Xeroderma Pigmentosum Patients.
S. Couve-Privat, B. Bouadjar, M. F. Avril, A. Sarasin, and L. Daya-Grosjean (2002)
Cancer Res. 62, 7186-7189
   Abstract »    Full Text »    PDF »
From the Cover: DE-cadherin-mediated cell adhesion is essential for maintaining somatic stem cells in the Drosophila ovary.
X. Song and T. Xie (2002)
PNAS 99, 14813-14818
   Abstract »    Full Text »    PDF »
Dissecting the Oncogenic Potential of Gli2: Deletion of an NH2-Terminal Fragment Alters Skin Tumor Phenotype.
H. Sheng, S. Goich, A. Wang, M. Grachtchouk, L. Lowe, R. Mo, K. Lin, F. J. de Sauvage, H. Sasaki, C.-c. Hui, et al. (2002)
Cancer Res. 62, 5308-5316
   Abstract »    Full Text »    PDF »
Several PATCHED1 Missense Mutations Display Activity in patched1-Deficient Fibroblasts.
E. C. Bailey, L. Milenkovic, M. P. Scott, J. F. Collawn, and R. L. Johnson (2002)
J. Biol. Chem. 277, 33632-33640
   Abstract »    Full Text »    PDF »
FOXM1 Is a Downstream Target of Gli1 in Basal Cell Carcinomas.
M.-T. Teh, S.-T. Wong, G. W. Neill, L. R. Ghali, M. P. Philpott, and A. G. Quinn (2002)
Cancer Res. 62, 4773-4780
   Abstract »    Full Text »    PDF »
EDD, the Human Hyperplastic Discs Protein, Has a Role in Progesterone Receptor Coactivation and Potential Involvement in DNA Damage Response.
M. J. Henderson, A. J. Russell, S. Hird, M. Munoz, J. L. Clancy, G. M. Lehrbach, S. T. Calanni, D. A. Jans, R. L. Sutherland, and C. K. W. Watts (2002)
J. Biol. Chem. 277, 26468-26478
   Abstract »    Full Text »    PDF »
Hedgehog-stimulated Phosphorylation of the Kinesin-related Protein Costal2 Is Mediated by the Serine/Threonine Kinase Fused.
K. E. Nybakken, C. W. Turck, D. J. Robbins, and J. M. Bishop (2002)
J. Biol. Chem. 277, 24638-24647
   Abstract »    Full Text »    PDF »
Unbalanced overexpression of the mutant allele in murine Patched mutants.
J. Calzada-Wack, R. Kappler, U. Schnitzbauer, T. Richter, M. Nathrath, M. Rosemann, S. N. Wagner, R. Hein, and H. Hahn (2002)
Carcinogenesis 23, 727-734
   Abstract »    Full Text »    PDF »
The Carboxyl-Terminal Domain of the Protein Kinase Fused Can Function as a Dominant Inhibitor of Hedgehog Signaling.
M. Ascano Jr., K. E. Nybakken, J. Sosinski, M. A. Stegman, and D. J. Robbins (2002)
Mol. Cell. Biol. 22, 1555-1566
   Abstract »    Full Text »    PDF »


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