MAGIC - Medulloblastoma Advanced Genomics International Consortium discover subgroups in childhood brain cancer
Research from the MAGIC project is anticipated to transform the way that children with medulloblastoma are treated. Funders of the project include Genome BC, Genome Canada, the Terry Fox Research Institute and other partners. “We congratulate this research team on this significant paper published today in Nature: this collaborative study, involving dozens of investigators and authors, sets an excellent example of how translational research can progress. For translational cancer research, where there is a lot of heterogeneity in the cancers being studied, working together is vital for accessing a large number of cases and for obtaining results more quickly," said Dr. Victor Ling, president and scientific director of the Terry Fox Research Institute.
“It is gratifying to see such rapid outcomes from this landmark project,” said Dr. Alan Winter, President and CEO of Genome BC. “This is genomics research in action -- project outcomes that directly lead to a change in clinical care -- and Genome BC is proud to be a part in such important work”.
Researchers at the GSC are conducting RNA, micro RNA and DNA sequencing for over 1,000 tissue samples obtained from children who have had medulloblastoma. Armed with this analysis the MAGIC team is basing its work around the understanding that medulloblastoma can be stratified into four distinct subgroups, each of which has a different prognosis when treated with chemotherapy, radiation and drug therapy. “We are very pleased that we have been able to produce such significant results so early in our study, and that we have the opportunity to disseminate our results in the journal Nature to the broader biomedical community,” said Dr. Marco Marra, Director of the GSC and project co-leader.
Identified as WNT, SHH, Groups 3 and 4, the published discoveries focus on Groups 3 and 4, which comprise patients with the worst prognosis. The article in Nature eloquently summarizes a large body of research, focusing on the molecular makeup of medulloblastoma cancer and identification of changes, specifically somatic copy number aberrations in each of the four subgroups. In Group 4 a gene associated with Parkinson’s disease is duplicated and in Group 3 another gene is translocated.
These events are significant, and scientists’ understanding of them offers potential treatment targets for patients classified in those groups.
To identify subgroup-specific therapies, the team is concentrating on identifying subgroup-specific drug targets, especially for those two groups with the worst prognosis. Currently the MAGIC group has identified potential drug targets which are specific to Group 3 medulloblastoma patients –- patients who are facing the worst prognosis. “What is even more exciting is the fact that therapies have already been developed and successfully tested against these targets for other types of cancer,” said Dr. Michael Taylor, project co-leader, senior author of the paper and pediatric neurosurgeon and scientist at SickKids.
Group 2 has also been analyzed and variations in DNA makeup identified will help with treatment as well. Group 1 identified no changes and typically has very good reactions to treatment and a healthier prognosis. “Acceptance by Nature for publication is a great honour and a real indicator that our work is headed in the right direction and of significance to other groups,” said Taylor. “Our research is getting closer to our ultimate goal -- making a difference in the lives of children who suffer from this devastating disease.”
Click on the following link to read or download the complete scientific article entitled "Subgroup-specific structural variation across 1,000 medulloblastoma genomes".
For further information contact:
Doris Sun, BA, MJ
Communications Officer - BC Cancer Agency
Provincial Health Services Authority
Phone: 604-675-8257
Citation with complete author list (*: BCCA - GSC authors): Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature (2012) doi:10.1038/nature11327. Published online 25 July 2012. 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 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
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