Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma (original) (raw)

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Sequence reads for GBM samples have been deposited in the European Genome Archive under accession number EGAS00001000226.

References

1. Faury, D. et al. Molecular profiling identifies prognostic subgroups of pediatric glioblastoma and shows increased YB-1 expression in tumors. J. Clin. Oncol. 25, 1196–1208 (2007)
   Article CAS Google Scholar
2. Haque, T. et al. Gene expression profiling from formalin-fixed paraffin-embedded tumors of pediatric glioblastoma. Clin. Cancer Res. 13, 6284–6292 (2007)
   Article MathSciNet CAS Google Scholar
3. Paugh, B. S. et al. Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J. Clin. Oncol. 28, 3061–3068 (2010)
   Article Google Scholar
4. Qu, H. Q. et al. Genome-wide profiling using single-nucleotide polymorphism arrays identifies novel chromosomal imbalances in pediatric glioblastomas. Neuro-oncol. 12, 153–163 (2010)
   Article CAS Google Scholar
5. Villard, L. et al. XNP mutation in a large family with Juberg-Marsidi syndrome. Nature Genet. 12, 359–360 (1996)
   Article CAS Google Scholar
6. Dhayalan, A. et al. The ATRX-ADD domain binds to H3 tail peptides and reads the combined methylation state of K4 and K9. Hum. Mol. Genet. 20, 2195–2203 (2011)
   Article CAS Google Scholar
7. Lewis, P. W., Elsaesser, S. J., Noh, K. M., Stadler, S. C. & Allis, C. D. Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres. Proc. Natl Acad. Sci. USA 107, 14075–14080 (2010)
   Article ADS CAS Google Scholar
8. Noushmehr, H. et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17, 510–522 (2010)
   Article CAS Google Scholar
9. Phillips, H. S. et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9, 157–173 (2006)
   Article CAS Google Scholar
10. The Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455 1061–1068 (2008) Medline CrssRef
11. Parsons, D. W. et al. An integrated genomic analysis of human glioblastoma multiforme. Science 321, 1807–1812 (2008)
    Article ADS CAS Google Scholar
12. Bax, D. A. et al. A distinct spectrum of copy number aberrations in pediatric high-grade gliomas. Clin. Cancer Res. 16, 3368–3377 (2010)
    Article CAS Google Scholar
13. Parsons, D. W. et al. The genetic landscape of the childhood cancer medulloblastoma. Science 331, 435–439 (2011)
    Article ADS CAS Google Scholar
14. Iwase, S. et al. ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome. Nature Struct. Mol. Biol. 18, 769–776 (2011)
    Article CAS Google Scholar
15. Goldberg, A. D. et al. Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140, 678–691 (2010)
    Article CAS Google Scholar
16. Wong, L. H. et al. ATRX interacts with H3.3 in maintaining telomere structural integrity in pluripotent embryonic stem cells. Genome Res. 20, 351–360 (2010)
    Article CAS Google Scholar
17. De La Fuente, R., Viveiros, M. M., Wigglesworth, K. & Eppig, J. J. ATRX, a member of the SNF2 family of helicase/ATPases, is required for chromosome alignment and meiotic spindle organization in metaphase II stage mouse oocytes. Dev. Biol. 272, 1–14 (2004)
    Article CAS Google Scholar
18. Verhaak, R. G. et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17, 98–110 (2010)
    Article CAS Google Scholar
19. Jiao, Y. et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331, 1199–1203 (2011)
    Article ADS CAS Google Scholar
20. Heaphy, C. M. et al. Altered telomeres in tumors with ATRX and DAXX mutations. Science 333, 425 (2011)
    Article ADS CAS Google Scholar
21. Chi, P., Allis, C. D. & Wang, G. G. Covalent histone modifications–miswritten, misinterpreted and mis-erased in human cancers. Nature Rev. Cancer 10, 457–469 (2010)
    Article CAS Google Scholar
22. Füllgrabe, J., Kavanagh, E. & Joseph, B. Histone onco-modifications. Oncogene 30, 3391–3403 (2011)
    Article Google Scholar
23. Talbert, P. B. & Henikoff, S. Histone variants–ancient wrap artists of the epigenome. Nature Rev. Mol. Cell Biol. 11, 264–275 (2010)
    Article CAS Google Scholar
24. Bernstein, B. E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315–326 (2006)
    Article CAS Google Scholar
25. Kolasinska-Zwierz, P. et al. Differential chromatin marking of introns and expressed exons by H3K36me3. Nature Genet. 41, 376–381 (2009)
    Article CAS Google Scholar
26. Edmunds, J. W., Mahadevan, L. C. & Clayton, A. L. Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation. EMBO J. 27, 406–420 (2008)
    Article CAS Google Scholar
27. Hakin-Smith, V. et al. Alternative lengthening of telomeres and survival in patients with glioblastoma multiforme. Lancet 361, 836–838 (2003)
    Article CAS Google Scholar
28. Yan, H. et al. IDH1 and IDH2 mutations in gliomas. N. Engl. J. Med. 360, 765–773 (2009)
    Article CAS Google Scholar
29. Dang, L. et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462, 739–744 (2009)
    Article ADS CAS Google Scholar
30. Cervera, A. M., Bayley, J. P., Devilee, P. & McCreath, K. J. Inhibition of succinate dehydrogenase dysregulates histone modification in mammalian cells. Mol. Cancer 8, 89 (2009)
    Article Google Scholar
31. Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009)
    Article CAS Google Scholar
32. Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009)
    Article Google Scholar
33. Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010)
    Article Google Scholar
34. Nakamura, K. et al. Sequence-specific error profile of Illumina sequences. Nucleic Acids Res. 39, e90 (2011)
    Article CAS Google Scholar
35. Peiffer, D. A. et al. High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping. Genome Res. 16, 1136–1148 (2006)
    Article CAS Google Scholar

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Acknowledgements

The authors are indebted to J. Rak, N. Sonenberg and C. Polychronakos for critical reading of this manuscript. D. M. Pearson, A. Wittmann, L. Sieber and L. Senf are acknowledged for technical assistance. This work was supported by the Cole Foundation, and was funded in part by Genome Canada and the Canadian Institute for Health Research (CIHR) with co-funding from Genome BC, Genome Quebec, CIHR-ICR (Institute for Cancer Research) and C17, through the Genome Canada/CIHR joint ATID Competition (project title: The Canadian Paediatric Cancer Genome Consortium: Translating next generation sequencing technologies into improved therapies for high-risk childhood cancer (NJ)), the Hungarian Scientific Research Fund (OTKA) Contract No. T-04639, the National Research and Development Fund (NKFP) Contract No. 1A/002/2004 (P.H., M.G., L.B.), the PedBrain project contributing to the International Cancer Genome Consortium funded by the German Cancer Aid (109252) and the CNS tumour tissue bank within the priority program on tumour tissue banking of the German Cancer Aid (108456), the BMBF, the Samantha Dickson Brain Tumour Trust, a grant from the National Cancer Center Heidelberg (“Paediatric Brain Tumor Preclinical Testing”), and a guest scientist stipend to M.R. from the German Cancer Research Center. X.-Y.L. and A.M.F. are the recipients of studentship awards from CIHR. K.J. is the recipient of a studentship from the Foundation of Stars. S.M.P. is the recipient of the Sybille Assmus Award for Neurooncology in 2009 and N.J. is the recipient of a Chercheur Boursier Award from Fonds de Recherche en Santé du Québec.

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Author notes

1. Jeremy Schwartzentruber, Andrey Korshunov and Xiao-Yang Liu: These authors contributed equally to this work.

Authors and Affiliations

1. McGill University and Genome Quebec Innovation Centre, Montreal, H3A 1A4, Quebec, Canada
   Jeremy Schwartzentruber, Pierre Lepage & Alexandre Montpetit
2. Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany,
   Andrey Korshunov & Andreas von Deimling
3. Departments of Human Genetics and Experimental Medicine, McGill University, Montreal, H3Z 2Z3, Canada,
   Xiao-Yang Liu, Karine Jacob, Adam M. Fontebasso, Dong-Anh Khuong Quang, Damien Faury, Jacek Majewski & Nada Jabado
4. Division of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany,
   David T. W. Jones, Elke Pfaff, Dominik Sturm, Marcel Kool, Hendrik Witt & Stefan M. Pfister
5. Division of Molecular Genetics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany,
   Martje Tönjes, Volker Hovestadt, Marc Zapatka & Peter Lichter
6. Department of Pathology, Montreal Children’s Hospital, McGill University Health Center, Montreal, Quebec H3H 1P3, Canada,
   Steffen Albrecht
7. Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec H4P 2R2, Canada,
   Andre Nantel
8. Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany,
   Carolin Konermann, Anders Lindroth & Christoph Plass
9. Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany,
   Natalie Jäger
10. European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany,
    Tobias Rausch & Jan O. Korbel
11. Department of Neuropathology, Burdenko Neurosurgical Institute, 125047 Moscow, Russia,
    Marina Ryzhova
12. Division of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
    Thomas Hielscher
13. 2nd Department of Paediatrics, Semmelweis University, Budapest, H-1094 Hungary
    Peter Hauser & Miklos Garami
14. Department of Neurosurgery, Medical and Health Science Center, University of Debrecen, Debrecen, H-4032 Hungary
    Almos Klekner & Laszlo Bognar
15. Department of Hematology and Oncology, Children’s University Hospital, 72076 Tübingen, Germany,
    Martin Ebinger
16. Department of Neurosurgery, University Hospital, 72076 Tübingen, Germany,
    Martin U. Schuhmann
17. Cnopfsche Kinderklinik, Nuremberg Children’s Hospital, 90419 Nuremberg, Germany,
    Wolfram Scheurlen
18. Prof. Hess Children’s Hospital, 28177 Bremen, Germany,
    Arnulf Pekrun
19. Klinikum Augsburg, Augsburg Children’s Hospital, 86156 Augsburg, Germany,
    Michael C. Frühwald
20. Department of Neuropathology, Institute of Pathology, University of Würzburg, 97080 Würzburg, Germany,
    Wolfgang Roggendorf
21. University Children’s Hospital, 06097 Halle, Germany,
    Christoph Kramm
22. University Children’s Hospital, 68167 Mannheim, Germany,
    Matthias Dürken
23. Department of Surgery, Division of Neurosurgery, Montreal Children’s Hospital, McGill University Health Centre, Montreal, Quebec H3H 1P3, Canada,
    Jeffrey Atkinson
24. Department of Molecular Pathology and Neuropathology, Medical University of Lodz, 92-216 Poland,
    Magdalena Zakrzewska & Pawel P. Liberski
25. Department of Neurosurgery, Polish Mother’s Memorial Hospital Research Institute, Lodz, 93-338 Poland,
    Krzystof Zakrzewski
26. Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3A 1A3, Canada,
    Zhifeng Dong & Peter Siegel
27. Department of Paediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, 69120 Heidelberg, Germany,
    Andreas E. Kulozik, Hendrik Witt, Till Milde, Olaf Witt & Stefan M. Pfister
28. The Arthur and Sonia Labatt Brain Tumor Research Centre, Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario M5G1X8, Canada,
    Abhijit Guha, Cindy Zhang, Pedro Castelo-Branco & Uri Tabori
29. Division of Hematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada,
    David Malkin & Uri Tabori
30. Department of Neuropathology, Heinrich-Heine-University, 40225 Düsseldorf, Germany,
    Jörg Felsberg & Guido Reifenberger
31. Department of Neuropathology, Heidelberg University Hospital, 69120 Heidelberg Germany,
    Andreas von Deimling
32. Division of Molecular Histopathology, Department of Pathology, University of Cambridge, CB2 0QQ, UK
    Koichi Ichimura & V. Peter Collins
33. Clinical Cooperation Unit Paediatric Oncology, German Cancer Research Center, 69120 Heidelberg, Germany,
    Till Milde & Olaf Witt
34. Department of Paediatrics, McGill University and the McGill University Health Center Research Institute, Montreal, Quebec H3Z 2Z3, Canada,
    Nada Jabado

Authors

1. Jeremy Schwartzentruber
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2. Andrey Korshunov
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3. Xiao-Yang Liu
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4. David T. W. Jones
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5. Elke Pfaff
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6. Karine Jacob
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7. Dominik Sturm
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8. Adam M. Fontebasso
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9. Dong-Anh Khuong Quang
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10. Martje Tönjes
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11. Volker Hovestadt
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12. Steffen Albrecht
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13. Marcel Kool
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14. Andre Nantel
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15. Carolin Konermann
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16. Anders Lindroth
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17. Natalie Jäger
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18. Tobias Rausch
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19. Marina Ryzhova
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20. Jan O. Korbel
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21. Thomas Hielscher
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22. Peter Hauser
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23. Miklos Garami
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24. Almos Klekner
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25. Laszlo Bognar
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26. Martin Ebinger
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27. Martin U. Schuhmann
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28. Wolfram Scheurlen
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29. Arnulf Pekrun
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30. Michael C. Frühwald
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31. Wolfgang Roggendorf
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32. Christoph Kramm
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33. Matthias Dürken
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34. Jeffrey Atkinson
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35. Pierre Lepage
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36. Alexandre Montpetit
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37. Magdalena Zakrzewska
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38. Krzystof Zakrzewski
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39. Pawel P. Liberski
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40. Zhifeng Dong
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41. Peter Siegel
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42. Andreas E. Kulozik
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43. Marc Zapatka
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44. Abhijit Guha
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45. David Malkin
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46. Jörg Felsberg
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47. Guido Reifenberger
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48. Andreas von Deimling
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49. Koichi Ichimura
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50. V. Peter Collins
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51. Hendrik Witt
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52. Till Milde
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53. Olaf Witt
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54. Cindy Zhang
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55. Pedro Castelo-Branco
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56. Peter Lichter
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57. Damien Faury
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58. Uri Tabori
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59. Christoph Plass
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60. Jacek Majewski
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61. Stefan M. Pfister
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62. Nada Jabado
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Contributions

A.K., X.-Y.L., D.T.W.J., E.P., D.-A.K.Q., S.A., M.T., Z.D., P.S., N. Jäger, H.W., T.M., C.Z., U.T., P.C.-B., D.F., P.L. and A.M. performed experimental work. X.-Y.L., J.S., J.M., D.T.W.J., M.K., D.M., V.H., K.J., A.M.F., D.S., A.N., C.K., A.L., A.K., T.R., J.M., J.O.K., T.H., P.L., C.P., S.M.P. and N. Jabado performed data analyses and produced the text and figures. M.R., M.E., M.U.S., W.S., A.P. and M.C.F., W.R., C.K., M.D., J.A., P.H., M.G., L.B., P.P.L., M. Zakrzewska, K.Z., A.E.K., M. Zapatka, A.G., A.K., G.R., J.F., A.v.D., K.I., V.P.C. and O.W. collected data and provided patient materials. J.M., S.M.P. and N. Jabado provided leadership for the project. All authors contributed to the final manuscript.

Corresponding authors

Correspondence toJacek Majewski, Stefan M. Pfister or Nada Jabado.

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The authors declare no competing financial interests.

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Schwartzentruber, J., Korshunov, A., Liu, XY. et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.Nature 482, 226–231 (2012). https://doi.org/10.1038/nature10833

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• Received: 21 August 2011
• Accepted: 05 January 2012
• Published: 29 January 2012
• Issue Date: 09 February 2012
• DOI: https://doi.org/10.1038/nature10833