Subgroup-specific structural variation across 1,000 medulloblastoma genomes Journal Article
| Authors: | Northcott, P. A.; Shih, D. J. H.; Peacock, J.; Garzia, L.; Sorana Morrissy, A.; Zichner, T.; Stútz, A. M.; Korshunov, A.; Reimand, J.; Schumacher, S. E.; Beroukhim, R.; Ellison, D. W.; Marshall, C. R.; Lionel, A. C.; MacK, S.; Dubuc, A.; Yao, Y.; Ramaswamy, V.; Luu, B.; Rolider, A.; Cavalli, F. M. G.; Wang, X.; Remke, M.; Wu, X.; Chiu, R. Y. B.; Chu, A.; Chuah, E.; Corbett, R. D.; Hoad, G. R.; Jackman, S. D.; Li, Y.; Lo, A.; Mungall, K. L.; Ming Nip, K.; Qian, J. Q.; Raymond, A. G. J.; Thiessen, N.; Varhol, R. J.; Birol, I.; Moore, R. A.; Mungall, A. J.; Holt, R.; Kawauchi, D.; Roussel, M. F.; Kool, M.; Jones, D. T. W.; Witt, H.; Fernandez-L, A.; Kenney, A. M.; Wechsler-Reya, R. J.; Dirks, P.; Aviv, T.; Grajkowska, W. A.; Perek-Polnik, M.; Haberler, C. C.; Delattre, O.; Reynaud, S. S.; Doz, F. F.; Pernet-Fattet, S. S.; Cho, B. K.; Kim, S. K.; Wang, K. C.; Scheurlen, W.; Eberhart, C. G.; Fèvre-Montange, M.; Jouvet, A.; Pollack, I. F.; Fan, X.; Muraszko, K. M.; Yancey Gillespie, G.; Di Rocco, C.; Massimi, L.; Michiels, E. M. C.; Kloosterhof, N. K.; French, P. J.; Kros, J. M.; Olson, J. M.; Ellenbogen, R. G.; Zitterbart, K.; Kren, L.; Thompson, R. C.; Cooper, M. K.; Lach, B.; McLendon, R. E.; Bigner, D. D.; Fontebasso, A.; Albrecht, S.; Jabado, N.; Lindsey, J. C.; Bailey, S.; Gupta, N.; Weiss, W. A.; Bognár, L.; Klekner, A.; Van Meter, T. E.; Kumabe, T.; Tominaga, T.; Elbabaa, S. K.; Leonard, J. R.; Rubin, J. B. |
| Article Title: | Subgroup-specific structural variation across 1,000 medulloblastoma genomes |
| Abstract: | Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy. © 2012 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | signal transduction; child; carrier protein; unclassified drug; oncoprotein; gene translocation; genetics; nonhuman; chemotherapy; proteins; metabolism; disease association; gene expression; classification; transforming growth factor beta; sonic hedgehog protein; hedgehog proteins; nerve tissue proteins; protein; genetic variability; immunoglobulin enhancer binding protein; radiation exposure; cancer genetics; human genome; myc protein; genes, myc; nf-kappa b; medulloblastoma; carrier proteins; membrane protein; oncogene proteins, fusion; molecular analysis; gene duplication; genomics; translocation, genetic; genome; tumor; parkinson disease; nerve protein; cerebellar neoplasms; medicine; mental health; oncogene myc; genome, human; disease treatment; child health; dna copy number variations; translocation; copy number variation; cerebellum tumor; chromosome disorder; shh protein, human; chromothripsis; ndrg1 protein; pvt1 protein; pvt1 protein, human; sncaip protein, human; chemical parameters; somatic copy number aberration; genomic structural variation |
| Journal Title: | Nature |
| Volume: | 487 |
| Issue: | 7409 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2012-08-02 |
| Start Page: | 49 |
| End Page: | 56 |
| Language: | English |
| DOI: | 10.1038/nature11327 |
| PROVIDER: | scopus |
| PUBMED: | 22832581 |
| PMCID: | PMC3683624 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 September 2012" - "CODEN: NATUA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work