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

Authors:
Paul A Northcott David J H Shih John Peacock Livia Garzia A Sorana Morrissy Thomas Zichner Adrian M Stütz Andrey Korshunov Jüri Reimand Steven E Schumacher Rameen Beroukhim David W Ellison Christian R Marshall Anath C Lionel Stephen Mack Adrian Dubuc Yuan Yao Vijay Ramaswamy Betty Luu Adi Rolider Florence M G Cavalli Xin Wang Marc Remke Xiaochong Wu Readman Y B Chiu Andy Chu Eric Chuah Richard D Corbett Gemma R Hoad Shaun D Jackman Yisu Li Allan Lo Karen L Mungall Ka Ming Nip Jenny Q Qian Anthony G J Raymond Nina T Thiessen Richard J Varhol Inanc Birol Richard A Moore Andrew J Mungall Robert Holt Daisuke Kawauchi Martine F Roussel Marcel Kool David T W Jones Hendrick Witt Africa Fernandez-L Anna M Kenney Robert J Wechsler-Reya Peter Dirks Tzvi Aviv Wieslawa A Grajkowska Marta Perek-Polnik Christine C Haberler Olivier Delattre Stéphanie S Reynaud François F Doz Sarah S Pernet-Fattet Byung-Kyu Cho Seung-Ki Kim Kyu-Chang Wang Wolfram Scheurlen Charles G Eberhart Michelle Fèvre-Montange Anne Jouvet Ian F Pollack Xing Fan Karin M Muraszko G Yancey Gillespie Concezio Di Rocco Luca Massimi Erna M C Michiels Nanne K Kloosterhof Pim J French Johan M Kros James M Olson Richard G Ellenbogen Karel Zitterbart Leos Kren Reid C Thompson Michael K Cooper Boleslaw Lach Roger E McLendon Darell D Bigner Adam Fontebasso Steffen Albrecht Nada Jabado Janet C Lindsey Simon Bailey Nalin Gupta William A Weiss László Bognár Almos Klekner Timothy E Van Meter Toshihiro Kumabe Teiji Tominaga Samer K Elbabaa Jeffrey R Leonard Joshua B Rubin Linda M Liau Erwin G Van Meir Maryam Fouladi Hideo Nakamura Giuseppe Cinalli Miklós Garami Peter Hauser Ali G Saad Achille Iolascon Shin Jung Carlos G Carlotti Rajeev Vibhakar Young Shin Ra Shenandoah Robinson Massimo Zollo Claudia C Faria Jennifer A Chan Michael L Levy Poul H B Sorensen Matthew Meyerson Scott L Pomeroy Yoon-Jae Cho Gary D Bader Uri Tabori Cynthia E Hawkins Eric Bouffet Stephen W Scherer James T Rutka David Malkin Steven C Clifford Steven J M Jones Jan O Korbel Stefan M Pfister Marco A Marra Michael D Taylor

Nature 2012 Aug;488(7409):49-56

Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada.

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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August 2012
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