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PATCHED-ONE or SMOOTHENED Gene Mutations Are Infrequent in Chondrosarcoma

  • Symposium: Molecular Genetics in Sarcoma
  • Published:
Clinical Orthopaedics and Related Research

An Erratum to this article was published on 22 October 2009

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References

  1. Berman DM, Karhadkar SS, Hallahan AR, Pritchard JI, Eberhart CG, Watkins DN, Chen JK, Cooper MK, Taipale J, Olson JM, Beachy PA. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science. 2002;297:1559–1561.

    Article  CAS  PubMed  Google Scholar 

  2. Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, Parker AR, Shimada Y, Eshleman JR, Watkins DN, Beachy PA. Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours. Nature. 2003;425:846–851.

    Article  CAS  PubMed  Google Scholar 

  3. Bovee JV, van den Broek LJ, Cleton-Jansen AM, Hogendoorn PC. Up-regulation of PTHrP and Bcl-2 expression characterizes the progression of osteochondroma towards peripheral chondrosarcoma and is a late event in central chondrosarcoma. Lab Invest. 2000;80:1925–1934.

    Article  CAS  PubMed  Google Scholar 

  4. Duman-Scheel M, Weng L, Xin S, Du W. Hedgehog regulates cell growth and proliferation by inducing Cyclin D and Cyclin E. Nature. 2002;417:299–304.

    Article  CAS  PubMed  Google Scholar 

  5. Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell. 1996;85:841–851.

    Article  CAS  PubMed  Google Scholar 

  6. Hammerschmidt M, Brook A, McMahon AP. The world according to hedgehog. Trends Genet. 1997;13:14–21.

    Article  CAS  PubMed  Google Scholar 

  7. Hooper JE, Scott MP. Communicating with hedgehogs. Nat Rev Mol Cell Biol. 2005;6:306–317.

    Article  CAS  PubMed  Google Scholar 

  8. Hopyan S, Gokgoz N, Poon R, Gensure RC, Yu C, Cole WG, Bell RS, Jüppner H, Andrulis IL, Wunder JS, Alman BA. A mutant PTH/PTHrP type I receptor in enchondromatosis. Nat Genet. 2002;30:306–310.

    Article  PubMed  Google Scholar 

  9. Hopyan S, Nadesan P, Yu C, Wunder J, Alman BA. Dysregulation of hedgehog signalling predisposes to synovial chondromatosis. J Pathol. 2005;206:143–150.

    Article  CAS  PubMed  Google Scholar 

  10. Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH Jr, Scott MP. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science. 1996;272:1668–1671.

    Article  CAS  PubMed  Google Scholar 

  11. Karhadkar SS, Bova GS, Abdallah N, Dhara S, Gardner D, Maitra A, Isaacs JT, Berman DM, Beachy PA. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature. 2004;431:707–712.

    Article  CAS  PubMed  Google Scholar 

  12. Katano M. Hedgehog signaling pathway as a therapeutic target in breast cancer. Cancer Lett. 2005;227:99–104.

    Article  CAS  PubMed  Google Scholar 

  13. Kindblom JM, Nilsson O, Hurme T, Ohlsson C, Savendahl L. Expression and localization of Indian hedgehog (IHH) and parathyroid hormone related protein (PTHrP) in the human growth plate during pubertal development. J Endocrinol. 2002;174:R1–R6.

    Article  CAS  PubMed  Google Scholar 

  14. Kobayashi T, Chung UI, Schipani E, Starbuck M, Karsenty G, Katagiri T, Goad DL, Lanske B, Kronenberg HM. PTHrP and Indian hedgehog control differentiation of growth plate chondrocytes at multiple steps. Development. 2002;129:2977–2986.

    CAS  PubMed  Google Scholar 

  15. Kronenberg HM. Developmental regulation of the growth plate. Nature. 2003;423:332–336.

    Article  CAS  PubMed  Google Scholar 

  16. Lam CW, Xie J, To KF, Ng HK, Lee KC, Yuen NW, Lim PL, Chan LY, Tong SF, McCormick F. A frequent activated smoothened mutation in sporadic basal cell carcinomas. Oncogene. 1999;18:833–836.

    Article  CAS  PubMed  Google Scholar 

  17. Lindstrom E, Shimokawa T, Toftgard R, Zaphiropoulos PG. PTCH mutations: distribution and analyses. Hum Mutat. 2006;27:215–219.

    Article  CAS  PubMed  Google Scholar 

  18. Minina E, Kreschel C, Naski MC, Ornitz DM, Vortkamp A. Interaction of FGF, Ihh/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation. Dev Cell. 2002;3:439–449.

    Article  CAS  PubMed  Google Scholar 

  19. Orita M, Suzuki Y, Sekiya T, Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989;5:874–879.

    Article  CAS  PubMed  Google Scholar 

  20. Pateder DB, Gish MW, O’Keefe RJ, Hicks DG, Teot LA, Rosier RN. Parathyroid hormone-related peptide expression in cartilaginous tumors. Clin Orthop Relat Res. 2002;403:198–204.

    Article  PubMed  Google Scholar 

  21. Provot S, Schipani E. Molecular mechanisms of endochondral bone development. Biochem Biophys Res Commun. 2005;328:658–665.

    Article  CAS  PubMed  Google Scholar 

  22. Raffel C, Jenkins RB, Frederick L, Hebrink D, Alderete B, Fults DW, James CD. Sporadic medulloblastomas contain PTCH mutations. Cancer Res. 1997;57:842–845.

    CAS  PubMed  Google Scholar 

  23. Reifenberger J, Wolter M, Knobbe CB, Köhler B, Schönicke A, Scharwächter C, Kumar K, Blaschke B, Ruzicka T, Reifenberger G. Somatic mutations in the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell carcinomas. Br J Dermatol. 2005;152:43–51.

    Article  CAS  PubMed  Google Scholar 

  24. Rohatgi R, Scott MP. Patching the gaps in Hedgehog signalling. Nat Cell Biol. 2007;9:1005–1009.

    Article  CAS  PubMed  Google Scholar 

  25. Romeo S, Bovee JV, Jadnanansing NA, Taminiau AH, Hogendoorn PC. Expression of cartilage growth plate signalling molecules in chondroblastoma. J Pathol. 2004;202:113–120.

    Article  CAS  PubMed  Google Scholar 

  26. Rozeman LB, Hameetman L, Cleton-Jansen AM, Taminiau AH, Hogendoorn PC, Bovee JV. Absence of IHH and retention of PTHrP signalling in enchondromas and central chondrosarcomas. J Pathol. 2005;205:476–482.

    Article  CAS  PubMed  Google Scholar 

  27. Rozeman LB, Sangiorgi L, Briaire-de Bruijn IH, Mainil-Varlet P, Bertoni F, Cleton-Jansen AM, Hogendoorn PC, Bovée JV. Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the PTHR1 mutation p.R150C. Hum Mutat. 2004;24:466–473.

    Article  CAS  PubMed  Google Scholar 

  28. Sanchez P, Clement V, Ruiz i Altaba A. Therapeutic targeting of the Hedgehog-GLI pathway in prostate cancer. Cancer Res. 2005;65:2990–2992.

    CAS  PubMed  Google Scholar 

  29. Silve C, Juppner H. Ollier disease. Orphanet J Rare Dis. 2006;1:37:1–6.

    Google Scholar 

  30. Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, Scott MP, Pennica D, Goddard A, Phillips H, Noll M, Hooper JE, de Sauvage F, Rosenthal A. The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature. 1996;384:129–134.

    Article  CAS  PubMed  Google Scholar 

  31. Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, Qi YP, Gysin S, Fernandez-del Castillo C, Yajnik V, Antoniu B, McMahon M, Warshaw AL, Hebrok M. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 2003;425:851–856.

    Article  CAS  PubMed  Google Scholar 

  32. Tiet TD, Hopyan S, Nadesan P, Gokgoz N, Poon R, Lin AC, Yan T, Andrulis IL, Alman BA, Wunder JS. Constitutive hedgehog signaling in chondrosarcoma up-regulates tumor cell proliferation. Am J Pathol. 2006;168:321–330.

    Article  CAS  PubMed  Google Scholar 

  33. Toftgard R, Chenevix-Trench G, Dean M. PTCH mutation database. Available at: www.cybergene.se/cgi-bin/w3-msql/ptchbase/index.html. Accessed December 28, 2007.

  34. Tostar U, Malm CJ, Meis-Kindblom JM, Kindblom LG, Toftgard R, Unden AB. Deregulation of the hedgehog signalling pathway: a possible role for the PTCH and SUFU genes in human rhabdomyoma and rhabdomyosarcoma development. J Pathol. 2006;208:17–25.

    Article  CAS  PubMed  Google Scholar 

  35. Unden AB, Holmberg E, Lundh-Rozell B, Stähle-Bäckdahl M, Zaphiropoulos PG, Toftgård R, Vorechovsky I. Mutations in the human homologue of Drosophila patched (PTCH) in basal cell carcinomas and the Gorlin syndrome: different in vivo mechanisms of PTCH inactivation. Cancer Res. 1996;56:4562–4565.

    CAS  PubMed  Google Scholar 

  36. Vorechovský I, Benediktsson KP, Toftgård R. The patched/hedgehog/smoothened signalling pathway in human breast cancer: no evidence for H133Y SHH, PTCH and SMO mutations. Eur J Cancer. 1999;35:711–713.

    Article  PubMed  Google Scholar 

  37. Walker EJ, Siminovitch KA. Primer: genomic and proteomic tools for the molecular dissection of disease. Nat Clin Pract Rheumatol. 2007;3:580–589.

    Article  CAS  PubMed  Google Scholar 

  38. Wicking C, Shanley S, Smyth I, Gillies S, Negus K, Graham S, Suthers G, Haites N, Edwards M, Wainwright B, Chenevix-Trench G. 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. 1997;60:21–26.

    CAS  PubMed  Google Scholar 

  39. Williams JA, Guicherit OM, Zaharian BI, Xu Y, Chai L, Wichterle H, Kon C, Gatchalian C, Porter JA, Rubin LL, Wang FY. Identification of a small molecule inhibitor of the hedgehog signaling pathway: effects on basal cell carcinoma-like lesions. Proc Natl Acad Sci USA. 2003;100:4616–4621.

    Article  CAS  PubMed  Google Scholar 

  40. Xie J, Johnson RL, Zhang X, Bare JW, Waldman FM, Cogen PH, Menon AG, Warren RS, Chen LC, Scott MP, Epstein EH Jr. Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors. Cancer Res. 1997;57:2369–2372.

    CAS  PubMed  Google Scholar 

  41. Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam CW, Hynes M, Goddard A, Rosenthal A, Epstein EH Jr, de Sauvage FJ. Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature. 1998;391:90–92.

    Article  CAS  PubMed  Google Scholar 

  42. Yuan Z, Goetz JA, Singh S, Ogden SK, Petty WJ, Black CC, Memoli VA, Dmitrovsky E, Robbins DJ. Frequent requirement of hedgehog signaling in non-small cell lung carcinoma. Oncogene. 2007;26:1046–1055.

    Article  CAS  PubMed  Google Scholar 

  43. Zhao Y, Tong C, Jiang J. Hedgehog regulates smoothened activity by inducing a conformational switch. Nature. 2007;450:252–258.

    Article  CAS  PubMed  Google Scholar 

  44. Zurawel RH, Allen C, Chiappa S, Cato W, Biegel J, Cogen P, de Sauvage F, Raffel C. Analysis of PTCH/SMO/SHH pathway genes in medulloblastoma. Genes Chromosomes Cancer. 2000;27:44–51.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Nalan Gokgoz for expert technical assistance.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Oncology, People’s Hospital, Beijing University, Beijing, China

    Taiqiang Yan MD

  2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Toronto, Canada

    Mark Angelini MD, FRCSC, Irene L. Andrulis PhD & Jay S. Wunder MD, MSc, FRCS(C)

  3. University Musculoskeletal Oncology Unit, Mount Sinai Hospital, University of Toronto, 476-600 University Avenue, Toronto, ON, Canada, M5G 1X5

    Mark Angelini MD, FRCSC & Jay S. Wunder MD, MSc, FRCS(C)

  4. Division of Orthopaedics and Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Canada

    Benjamin A. Alman MD, FRCSC

Authors
  1. Taiqiang Yan MD
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  2. Mark Angelini MD, FRCSC
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  3. Benjamin A. Alman MD, FRCSC
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  4. Irene L. Andrulis PhD
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  5. Jay S. Wunder MD, MSc, FRCS(C)
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Corresponding author

Correspondence to Jay S. Wunder MD, MSc, FRCS(C).

Additional information

One or more of the authors (TY, BAA, JSW) have received funding from the Canadian Institutes of Health Research [CIHR grant # 37913].

Each author certifies that his or her institution has approved or waived approval for the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

An erratum to this article can be found at http://dx.doi.org/10.1007/s11999-009-1134-x

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Yan, T., Angelini, M., Alman, B.A. et al. PATCHED-ONE or SMOOTHENED Gene Mutations Are Infrequent in Chondrosarcoma. Clin Orthop Relat Res 466, 2184–2189 (2008). https://doi.org/10.1007/s11999-008-0332-2

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  • DOI: https://doi.org/10.1007/s11999-008-0332-2

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