Subgroup-specific structural variation across 1,000 medulloblastoma genomes

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 v...

Full description

Bibliographic Details
Main 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.
Format:	Journal Article
Published:	2012
Online Access:	http://hdl.handle.net/20.500.11937/37424

_version_	1848755043381018624
author	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.
author_facet	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.
author_sort	Northcott, P.
building	Curtin Institutional Repository
collection	Online Access
description	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.
first_indexed	2025-11-14T08:50:02Z
format	Journal Article
id	curtin-20.500.11937-37424
institution	Curtin University Malaysia
institution_category	Local University
last_indexed	2025-11-14T08:50:02Z
publishDate	2012
recordtype	eprints
repository_type	Digital Repository
spelling	curtin-20.500.11937-374242019-02-19T05:35:06Z 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. 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. 2012 Journal Article http://hdl.handle.net/20.500.11937/37424 10.1038/nature11327 fulltext
spellingShingle	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. Subgroup-specific structural variation across 1,000 medulloblastoma genomes
title	Subgroup-specific structural variation across 1,000 medulloblastoma genomes
title_full	Subgroup-specific structural variation across 1,000 medulloblastoma genomes
title_fullStr	Subgroup-specific structural variation across 1,000 medulloblastoma genomes
title_full_unstemmed	Subgroup-specific structural variation across 1,000 medulloblastoma genomes
title_short	Subgroup-specific structural variation across 1,000 medulloblastoma genomes
title_sort	subgroup-specific structural variation across 1,000 medulloblastoma genomes
url	http://hdl.handle.net/20.500.11937/37424

Subgroup-specific structural variation across 1,000 medulloblastoma genomes

Similar Items