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High incidence of medulloblastoma following X-ray-irradiation of newborn Ptc1 heterozygous mice

Oncogene volume 21, pages 7580–7584 (2002)Cite this article

Abstract

Individuals affected with the Gorlin syndrome inherit a germ-line mutation of the patched (Ptc1) developmental gene and, analogously to Ptc1 heterozygous mice, show an increased susceptibility to spontaneous tumor development. Human and mouse Ptc1 heterozygotes (Ptc1+/−) are also hypersensitive to ionizing radiation (IR)-induced tumorigenesis in terms of basal cell carcinoma (BCC) induction. We have analysed the involvement of Ptc1 in the tumorigenic response to a single dose of 3 Gy X-rays in neonatal and adult Ptc1 heterozygous and wild type mice. We report that irradiation dramatically increased the incidence of medulloblastoma development (51%) over the spontaneous rate (7%) in neonatal but not adult Ptc1 heterozygotes, indicating that medulloblastoma induction by IR is subjected to temporal restriction. Analysis of Ptc1 allele status in the tumors revealed loss of the wild type allele in 17 of 18 medulloblastomas from irradiated mice and in two of three spontaneous medulloblastomas. To our knowledge, irradiated newborn Ptc1+/− heterozygous mice constitute the first mouse model of IR-induced medulloblastoma tumorigenesis, providing a useful tool to elucidate the molecular basis of medulloblastoma development.

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References

  • Aszterbaum M, Epstein J, Oro A, Douglas V, LeBott PE, Scott MP, Epstein Jr EH . 1999 Nat. Med. 11: 1285–1291

  • Barnes EA, Kong M, Oleendorff V, Donoghue DJ . 2001 EMBO J. 9: 2214–2223

  • Chidambaram A, Goldestein AM, Galiani MR, Gerrard B, Bale SJ, Digiovanna JJ, Bale AE, Dean M . 1996 Cancer Res. 56: 4599–4601

  • Corey R, Jenkins RB, Frederick L, Hebrink D, Alderete B, Fults DW, James CD . 1997 Cancer Res. 57: 842–845

  • Cowan R, Hoban P, Kelsey A, Birch JM, Gattamaneni R, Evans DG . 1997 Br. J. Cancer 76: 141–145

  • Goldowitz D, Hamre K . 1998 Trends Neurosci. 21: 375–382

  • Goodrich LV, Milenkovic L, Higgins KM, Scott MP . 1997 Science 277: 1109–1113

  • Gorlin RJ . 1987 Medicine (Baltimore) 66: 98–113

  • Hahn H, Wicking C, Zaphiropoulous PG, Galiani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldestein AM, Dean M, Tofgard R, Chenevix-Trench G, Wainwright B, Bale AE . 1996 Cell 85: 841–851

  • Hahn H, Wojnowski L, Zimmer AM, Hall J, Miller G, Zimmer A . 1998 Nat. Med. 4: 619–622

  • Innocente SA, Abrahamson JLA, Cogswell JP, Lee JM . 1999 Proc. Natl. Acad. Sci. USA 96: 2147–2152

  • Lacombe D, Chateil JF, Fontan D, Battin J . 1990 Genet. Couns. 1: 273–277

  • Martì E, Bovolenta P . 2002 Trends Neurosci. 25: 89–94

  • Miller DL, Weinstock MA . 1994 J. Am. Acad. Dermatol. 30: 774–778

  • Novakovic B . 1994 Mol. Pediatr. Oncol. 23: 480

  • Pappo AS, Shapiro DN, Crist WM . 1997 Pediatr. Clin. North. Am. 44: 953–972

  • Rowitch DH, St-Jacques B, Lee SMK, Flax JD, Snyder EY, McMahon AP . 1999 J. Neurosci. 19: 8954–8965

  • Unden AB, Holmberg E, Lundhrozell B, Stahlebackdahl M, Zaphiropoulos PG, Tofgard R, Vorechovsky I . 1996 Cancer Res. 56: 4562–4565

  • Wetmore C, Eberhart DE, Curran T . 2000 Cancer Res. 60: 2239–2246

  • Wetmore C, Eberhart DE, Curran T . 2001 Cancer Res. 61: 513–516

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

  • Xie J, Johnson RL, Zhang X, Bare JW, Waldman FM, Cogen PH, Menon AG, Warren RS, Chen LC, Scott MP, Epstein Jr EH . 1997 Cancer Res. 57: 2369–2372

  • Zurawel RH, Chiappa SA, Allen C, Raffel C . 1997 Cancer Res. 57: 842–845

  • Zurawel RH, Allen C, Wechsler-Reya R, Scott MP, Raffel C . 2000 Genes Chromosomes Cancer 28: 77–81

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Acknowledgements

This work was partially supported by the Commission of the European Communities under Contract FIGH-CT-1999-00006 and by Progetto Strategico 1998 (L. 449/97-MURST). The authors wish to thank Mrs M Manzotti for assistance in handling and treating the mice. Dr M Tanori was supported by a fellowship from Istituto Nazionale Tumori.

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Authors and Affiliations

  1. Bio-Technology Unit, ENEA CR-Casaccia, Rome, Italy

    Simonetta Pazzaglia, Mariateresa Mancuso, Simonetta Rebessi, Vincenzo Di Majo & Anna Saran

  2. Institute of Pathology, GSF National Research Center, Munich, Germany

    Michael J Atkinson

  3. Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy

    Mirella Tanori

  4. Radiation Protection Unit, ENEA CR-Casaccia, Rome, Italy

    Vincenzo Covelli

  5. Institute of Human Genetics, University of Goettingen, Goettingen, Germany

    Heidi Hahn

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  1. Simonetta Pazzaglia
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Correspondence to Simonetta Pazzaglia.

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Pazzaglia, S., Mancuso, M., Atkinson, M. et al. High incidence of medulloblastoma following X-ray-irradiation of newborn Ptc1 heterozygous mice. Oncogene 21, 7580–7584 (2002). https://doi.org/10.1038/sj.onc.1205973

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