Subtypes of medulloblastoma have distinct developmental origins (original) (raw)

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1. Ellison, D. W. et al. β-Catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children’s Cancer Study Group Brain Tumour Committee. J. Clin. Oncol. 23, 7951–7957 (2005)
   Article CAS Google Scholar
2. Gajjar, A. et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 7, 813–820 (2006)
   Article Google Scholar
3. Thompson, M. C. et al. Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J. Clin. Oncol. 24, 1924–1931 (2006)
   Article CAS Google Scholar
4. Kool, M. et al. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS ONE 3, e3088 (2008)
   Article ADS Google Scholar
5. Gilbertson, R. J. & Ellison, D. W. The origins of medulloblastoma subtypes. Annu. Rev. Pathol. 3, 341–365 (2008)
   Article CAS Google Scholar
6. Goodrich, L. V., Milenkovic, L., Higgins, K. M. & Scott, M. P. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277, 1109–1113 (1997)
   Article CAS Google Scholar
7. Schuller, U. et al. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14, 123–134 (2008)
   Article CAS Google Scholar
8. Yang, Z. J. et al. Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell 14, 135–145 (2008)
   Article CAS Google Scholar
9. Romer, J. T. et al. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1+/−p53−/− mice. Cancer Cell 6, 229–240 (2004)
   Article CAS Google Scholar
10. Rudin, C. M. et al. Treatment of medulloblastoma with Hedgehog pathway inhibitor GDC-0449. N. Engl. J. Med. 2, 1173–1178 (2009)
    Article Google Scholar
11. Louis, D., Ohgaki, H., Wiestler, O., Cavenee, W. (eds) World Health Organization Classification of Tumours of the Central Nervous System (International Agency for Research on Cancer, 2007)
    Google Scholar
12. Huang, X. et al. Transventricular delivery of Sonic hedgehog is essential to cerebellar ventricular zone development. Proc Natl Acad. Sci. USA 107, 8422–8427 (2010)
    Article ADS CAS Google Scholar
13. Johnson, R. A. et al. Cross-species genomics matches driver mutations and cell compartments to model ependymoma. Nature 466, 632–636 (2010)
    Article ADS CAS Google Scholar
14. Lee, Y. et al. A molecular fingerprint for medulloblastoma. Cancer Res. 63, 5428–5437 (2003)
    CAS PubMed Google Scholar
15. Ray, R. S. & Dymecki, S. M. Rautenlippe Redux—toward a unified view of the precerebellar rhombic lip. Curr. Opin. Cell Biol. 21, 741–747 (2009)
    Article CAS Google Scholar
16. Morales, D. & Hatten, M. E. Molecular markers of neuronal progenitors in the embryonic cerebellar anlage. J. Neurosci. 26, 12226–12236 (2006)
    Article CAS Google Scholar
17. Harada, N. et al. Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. EMBO J. 18, 5931–5942 (1999)
    Article CAS Google Scholar
18. Hegedus, B. et al. Neurofibromatosis-1 regulates neuronal and glial cell differentiation from neuroglial progenitors in vivo by both cAMP- and Ras-dependent mechanisms. Cell Stem Cell 1, 443–457 (2007)
    Article CAS Google Scholar
19. Storm, R. et al. The bHLH transcription factor Olig3 marks the dorsal neuroepithelium of the hindbrain and is essential for the development of brainstem nuclei. Development 136, 295–305 (2009)
    Article CAS Google Scholar
20. Jonkers, J. et al. Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nature Genet. 29, 418–425 (2001)
    Article CAS Google Scholar
21. Wetmore, C., Eberhart, D. E. & Curran, T. Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched. Cancer Res. 61, 513–516 (2001)
    CAS PubMed Google Scholar
22. Chenn, A. & Walsh, C. A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297, 365–369 (2002)
    Article ADS CAS Google Scholar
23. Landsberg, R. L. et al. Hindbrain rhombic lip is comprised of discrete progenitor cell populations allocated by Pax6. Neuron 48, 933–947 (2005)
    Article CAS Google Scholar
24. DiPietrantonio, H. J. & Dymecki, S. M. Zic1 levels regulate mossy fiber neuron position and axon laterality choice in the ventral brain stem. Neuroscience 162, 560–573 (2009)
    Article CAS Google Scholar
25. Farago, A. F., Awatramani, R. B. & Dymecki, S. M. Assembly of the brainstem cochlear nuclear complex is revealed by intersectional and subtractive genetic fate maps. Neuron 50, 205–218 (2006)
    Article CAS Google Scholar
26. Oliver, T. G. et al. Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma. Development 132, 2425–2439 (2005)
    Article CAS Google Scholar
27. Uziel, T. et al. The tumor suppressors Ink4c and p53 collaborate independently with Patched to suppress medulloblastoma formation. Genes Dev. 19, 2656–2667 (2005)
    Article CAS Google Scholar
28. Frappart, P. O. et al. Recurrent genomic alterations characterize medulloblastoma arising from DNA double-strand break repair deficiency. Proc. Natl Acad. Sci. USA 106, 1880–1885 (2009)
    Article ADS CAS Google Scholar
29. Ikeda, A., Ikeda, S., Gridley, T., Nishina, P. M. & Naggert, J. K. Neural tube defects and neuroepithelial cell death in Tulp3 knockout mice. Hum. Mol. Genet. 10, 1325–1334 (2001)
    Article CAS Google Scholar

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Acknowledgements

R.J.G. holds the Howard C. Schott Research Chair from the Malia’s Cord Foundation, and is supported by grants from the National Institutes of Health (R01CA129541, P01CA96832 and P30CA021765), the Collaborative Ependymoma Research Network and by the American Lebanese Syrian Associated Charities. We are grateful to A. Chenn, J. Johnson and C. Birchmeier for their gifts of reagents and the staff of the Hartwell Center for Bioinformatics and Biotechnology and ARC at St Jude Children’s Research Hospital for technical assistance.

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Authors and Affiliations

1. Department of Developmental Neurobiology, St Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, 38105, Tennessee, USA
   Paul Gibson, Yiai Tong, Giles Robinson, D. Spencer Currle, Christopher Eden, Tanya A. Kranenburg, Twala Hogg, Helen Poppleton, Julie Martin & Richard J. Gilbertson
2. Department of Oncology, St Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, 38105, Tennessee, USA
   Giles Robinson, Amar Gajjar & Richard J. Gilbertson
3. Hartwell Center for Bioinformatics and Biotechnology, St Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, 38105, Tennessee, USA
   David Finkelstein
4. Department of Biostatistics, St Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, 38105, Tennessee, USA
   Stanley Pounds
5. Department of Radiological Sciences, St Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, 38105, Tennessee, USA
   Zoltan Patay, Matthew Scoggins & Robert Ogg
6. Department of Genetics and Tumor Cell Biology, St Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, 38105, Tennessee, USA
   Youngsoo Lee, Frederique Zindy, Martine F. Roussel & Peter J. McKinnon
7. Department of Surgery, St Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, 38105, Tennessee, USA
   Frederick A. Boop & Robert A. Sanford
8. Department of Pathology, St Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, 38105, Tennessee, USA
   David W. Ellison
9. Department of Pediatric Hematology/Oncology, The Cleveland Clinic, 9500 Euclid Avenue/S20, Cleveland, 44195, Ohio, USA
   Margaret C. Thompson
10. Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, 08903, New Jersey, USA
    Aaron Weiss
11. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, 27710, North Carolina, USA
    Yanxin Pei, Zeng-Jie Yang, Sonja Brun & Robert Wechsler-Reya
12. Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Janet C. Lindsey & Steven C. Clifford
13. Graduate School of Medicine, Kyoto University, Yoshida-Konoé-cho, Sakyo, Kyoto 606-8501, Japan,
    Makoto M. Taketo
14. Department of Neurology, Washington University School of Medicine, St Louis, 63110, Missouri, USA
    David H. Gutmann

Authors

1. Paul Gibson
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2. Yiai Tong
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3. Giles Robinson
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4. Margaret C. Thompson
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5. D. Spencer Currle
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6. Christopher Eden
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7. Tanya A. Kranenburg
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8. Twala Hogg
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9. Helen Poppleton
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10. Julie Martin
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11. David Finkelstein
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12. Stanley Pounds
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13. Aaron Weiss
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14. Zoltan Patay
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15. Matthew Scoggins
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16. Robert Ogg
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17. Yanxin Pei
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18. Zeng-Jie Yang
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19. Sonja Brun
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20. Youngsoo Lee
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21. Frederique Zindy
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22. Janet C. Lindsey
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23. Makoto M. Taketo
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24. Frederick A. Boop
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25. Robert A. Sanford
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26. Amar Gajjar
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27. Steven C. Clifford
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28. Martine F. Roussel
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29. Peter J. McKinnon
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30. David H. Gutmann
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31. David W. Ellison
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32. Robert Wechsler-Reya
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33. Richard J. Gilbertson
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Contributions

R.J.G. conceived the research and planned experiments. P.G. also planned and conducted most of the experiments. Y.T., G.R., D.S.C., M.C.T., T.H., H.P., J.M., J.C.L., Y.L., F.Z., C.E., S.C.C., M.F.R., P.J.M. and R.W.-R. conducted experiments. D.F. and S.P. provided bioinformatic expertise. A.G., F.A.B. and R.A.S. provided clinical advice and tumour samples. D.H.G. provided the Blbp-Cre mouse and data. M.M.T. provided the Ctnnb1 lox(ex3)/lox(ex3) mouse. Z.P. and R.O. reviewed and analysed the human MRI scans. D.W.E. provided pathology review. All authors contributed to writing the manuscript.

Corresponding author

Correspondence toRichard J. Gilbertson.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

The file contains Supplementary Methods, additional references, Supplementary Figures 1-14 with legends and Supplementary Table 1. (PDF 12061 kb)

Supplementary Dataset 1

This dataset reports the expression distribution in the developing mouse hindbrain (rhombomeres 1-8) of 24 and 25 signature genes of human WNT-subgroup and SHH-subgroup medulloblastoma respectfully. (PDF 30323 kb)

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Gibson, P., Tong, Y., Robinson, G. et al. Subtypes of medulloblastoma have distinct developmental origins.Nature 468, 1095–1099 (2010). https://doi.org/10.1038/nature09587

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• Received: 26 September 2009
• Accepted: 15 October 2010
• Published: 08 December 2010
• Issue Date: 23 December 2010
• DOI: https://doi.org/10.1038/nature09587