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ARTICLE
doi:10.1038/nature11213
Novel mutations target distinct
subgroups of medulloblastoma
Giles Robinson1,2,3*, Matthew Parker1,4*, Tanya A. Kranenburg1,2*, Charles Lu1,5, Xiang Chen1,4, Li Ding1,5,6 ,
Timothy N. Phoenix1,2, Erin Hedlund1,4, Lei Wei1,4,7, Xiaoyan Zhu1,2, Nader Chalhoub1,2, Suzanne J. Baker1,2, Robert Huether1,4,8 ,
Richard Kriwacki1,8, Natasha Curley1,2, Radhika Thiruvenkatam1,2, Jianmin Wang1,9, Gang Wu1,4, Michael Rusch1,4, Xin Hong1,5,
Jared Becksfort1,9, Pankaj Gupta1,9, Jing Ma1,7, John Easton1,4, Bhavin Vadodaria1,4, Arzu Onar-Thomas1,10 , Tong Lin1,10,
Shaoyi Li1,10 , Stanley Pounds1,10 , Steven Paugh1,11 , David Zhao1,9, Daisuke Kawauchi1,12 , Martine F. Roussel1,12 ,
David Finkelstein1,4, David W. Ellison1,7, Ching C. Lau1,13 , Eric Bouffet1,14 , Tim Hassall1,15, Sridharan Gururangan1,16 ,
Richard Cohn1,17, Robert S. Fulton1,5,6 , Lucinda L. Fulton1,5,6 , David J. Dooling1,5,6 , Kerri Ochoa1,5,6 , Amar Gajjar1,3,
Elaine R. Mardis1,5,6,18 , Richard K. Wilson1,5,6,19, James R. Downing1,7, Jinghui Zhang1,4 Richard J. Gilbertson1,2,3
Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. Here, to identify mutations
that drive medulloblastoma, we sequenced the entire genomes of 37 tumours and matched normal blood. One-hundred
and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56
medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma; several
target distinct components of the epigenetic machinery in different disease subgroups, such as regulators of H3K27
and H3K4 trimethylation in subgroups 3 and 4 (for example, KDM6A and ZMYM3), and CTNNB1-associated chromatin
re
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