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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • August 2012

Published In

Volume / Issue

  • 488 / 7409

Start / End Page

  • 49 - 56

PubMed ID

  • 22832581

Pubmed Central ID

  • 22832581

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature11327

Language

  • eng