Subgroup-specific structural variation across 1,000 medulloblastoma genomes

Northcott, P.; Shih, D.; Peacock, J.; Garzia, L.; Sorana Morrissy, A.; Zichner, T.; Stútz, A.; Korshunov, A.; Reimand, J.; Schumacher, S.; Beroukhim, R.; Ellison, D.; Marshall, C.; Lionel, A.; MacK, S.; Dubuc, A.; Yao, Y.; Ramaswamy, V.; Luu, B.; Rolider, A.; Cavalli, F.; Wang, X.; Remke, M.; Wu, X.; Chiu, R.; Chu, A.; Chuah, E.; Corbett, R.; Hoad, G.; Jackman, S.; Li, Y.; Lo, A.; Mungall, K.; Ming Nip, K.; Qian, J.; Raymond, A.; Thiessen, N.; Varhol, Richard; Birol, I.; Moore, R.; Mungall, A.; Holt, R.; Kawauchi, D.; Roussel, M.; Kool, M.; Jones, D.; Witt, H.; Fernandez-L, A.; Kenney, A.; Wechsler-Reya, R.; Dirks, P.; Aviv, T.; Grajkowska, W.; Perek-Polnik, M.; Haberler, C.; Delattre, O.; Reynaud, S.; Doz, F.; Pernet-Fattet, S.; Cho, B.; Kim, S.; Wang, K.; Scheurlen, W.; Eberhart, C.; Fèvre-Montange, M.; Jouvet, A.; Pollack, I.; Fan, X.; Muraszko, K.; Yancey Gillespie, G.; Di Rocco, C.; Massimi, L.; Michiels, E.; Kloosterhof, N.; French, P.; Kros, J.; Olson, J.; Ellenbogen, R.; Zitterbart, K.; Kren, L.; Thompson, R.; Cooper, M.

doi:10.1038/nature11327

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Access Status

Open access

Authors

Northcott, P.

Shih, D.

Peacock, J.

Garzia, L.

Sorana Morrissy, A.

Zichner, T.

Stútz, A.

Korshunov, A.

Reimand, J.

Schumacher, S.

Beroukhim, R.

Ellison, D.

Marshall, C.

Lionel, A.

MacK, S.

Dubuc, A.

Yao, Y.

Ramaswamy, V.

Luu, B.

Rolider, A.

Cavalli, F.

Wang, X.

Remke, M.

Wu, X.

Chiu, R.

Chu, A.

Chuah, E.

Corbett, R.

Hoad, G.

Jackman, S.

Li, Y.

Lo, A.

Mungall, K.

Ming Nip, K.

Qian, J.

Raymond, A.

Thiessen, N.

Varhol, Richard

Birol, I.

Moore, R.

Mungall, A.

Holt, R.

Kawauchi, D.

Roussel, M.

Kool, M.

Jones, D.

Witt, H.

Fernandez-L, A.

Kenney, A.

Wechsler-Reya, R.

Dirks, P.

Aviv, T.

Grajkowska, W.

Perek-Polnik, M.

Haberler, C.

Delattre, O.

Reynaud, S.

Doz, F.

Pernet-Fattet, S.

Cho, B.

Kim, S.

Wang, K.

Scheurlen, W.

Eberhart, C.

Fèvre-Montange, M.

Jouvet, A.

Pollack, I.

Fan, X.

Muraszko, K.

Yancey Gillespie, G.

Di Rocco, C.

Massimi, L.

Michiels, E.

Kloosterhof, N.

French, P.

Kros, J.

Olson, J.

Ellenbogen, R.

Zitterbart, K.

Kren, L.

Thompson, R.

Cooper, M.

Date

2012

Type

Journal Article

Metadata

Show full item record

Citation

Northcott, P. and Shih, D. and Peacock, J. and Garzia, L. and Sorana Morrissy, A. and Zichner, T. and Stútz, A. et al. 2012. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature. 487 (7409): pp. 49-56.

Source Title

Nature

DOI

10.1038/nature11327

ISSN

0028-0836

School

Department of Health Policy and Management

Remarks

This open access article is distributed under the Creative Commons license http://doi.org/10.1038/nature11327

URI

http://hdl.handle.net/20.500.11937/37424

Collection

Curtin Research Publications

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 4a. 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-ß signalling in Group 3, and NF-?B signalling in Group 4, suggest future avenues for rational, targeted therapy. © 2012 Macmillan Publishers Limited. All rights reserved.