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Subgroup-specific structural variation across 1,000 medulloblastoma genomes.

Publication ,  Journal Article
Northcott, PA; Shih, DJH; Peacock, J; Garzia, L; Morrissy, AS; Zichner, T; Stütz, AM; Korshunov, A; Reimand, J; Schumacher, SE; Beroukhim, R ...
Published in: Nature
August 2, 2012

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.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

August 2, 2012

Volume

488

Issue

7409

Start / End Page

49 / 56

Location

England

Related Subject Headings

  • Translocation, Genetic
  • Transforming Growth Factor beta
  • Signal Transduction
  • RNA, Long Noncoding
  • Proteins
  • Oncogene Proteins, Fusion
  • Nerve Tissue Proteins
  • NF-kappa B
  • Medulloblastoma
  • Humans
 

Citation

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Chicago
ICMJE
MLA
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Northcott, P. A., Shih, D. J. H., Peacock, J., Garzia, L., Morrissy, A. S., Zichner, T., … Taylor, M. D. (2012). Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature, 488(7409), 49–56. https://doi.org/10.1038/nature11327
Northcott, Paul A., David J. H. Shih, John Peacock, Livia Garzia, A Sorana Morrissy, Thomas Zichner, Adrian M. Stütz, et al. “Subgroup-specific structural variation across 1,000 medulloblastoma genomes.Nature 488, no. 7409 (August 2, 2012): 49–56. https://doi.org/10.1038/nature11327.
Northcott PA, Shih DJH, Peacock J, Garzia L, Morrissy AS, Zichner T, et al. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature. 2012 Aug 2;488(7409):49–56.
Northcott, Paul A., et al. “Subgroup-specific structural variation across 1,000 medulloblastoma genomes.Nature, vol. 488, no. 7409, Aug. 2012, pp. 49–56. Pubmed, doi:10.1038/nature11327.
Northcott PA, Shih DJH, Peacock J, Garzia L, Morrissy AS, Zichner T, Stütz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FMG, Wang X, Remke M, Wu X, Chiu RYB, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AGJ, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DTW, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho B-K, Kim S-K, Wang K-C, Scheurlen W, Eberhart CG, Fèvre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EMC, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognár L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PHB, Meyerson M, Pomeroy SL, Cho Y-J, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJM, Korbel JO, Pfister SM, Marra MA, Taylor MD. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature. 2012 Aug 2;488(7409):49–56.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

August 2, 2012

Volume

488

Issue

7409

Start / End Page

49 / 56

Location

England

Related Subject Headings

  • Translocation, Genetic
  • Transforming Growth Factor beta
  • Signal Transduction
  • RNA, Long Noncoding
  • Proteins
  • Oncogene Proteins, Fusion
  • Nerve Tissue Proteins
  • NF-kappa B
  • Medulloblastoma
  • Humans