Novel mutations target distinct subgroups of medulloblastoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-08

AUTHORS

Giles Robinson, Matthew Parker, Tanya A. Kranenburg, Charles Lu, Xiang Chen, Li Ding, Timothy N. Phoenix, Erin Hedlund, Lei Wei, Xiaoyan Zhu, Nader Chalhoub, Suzanne J. Baker, Robert Huether, Richard Kriwacki, Natasha Curley, Radhika Thiruvenkatam, Jianmin Wang, Gang Wu, Michael Rusch, Xin Hong, Jared Becksfort, Pankaj Gupta, Jing Ma, John Easton, Bhavin Vadodaria, Arzu Onar-Thomas, Tong Lin, Shaoyi Li, Stanley Pounds, Steven Paugh, David Zhao, Daisuke Kawauchi, Martine F. Roussel, David Finkelstein, David W. Ellison, Ching C. Lau, Eric Bouffet, Tim Hassall, Sridharan Gururangan, Richard Cohn, Robert S. Fulton, Lucinda L. Fulton, David J. Dooling, Kerri Ochoa, Amar Gajjar, Elaine R. Mardis, Richard K. Wilson, James R. Downing, Jinghui Zhang, Richard J. Gilbertson

ABSTRACT

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-modellers in WNT-subgroup tumours (for example, SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours identified genes that maintain this cell lineage (DDX3X), as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumorigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development. More... »

PAGES

43

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature11213

DOI

http://dx.doi.org/10.1038/nature11213

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1040240428

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22722829


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