Journal article
Clonal selection drives genetic divergence of metastatic medulloblastoma
Nature (London), Vol.482(7386), pp.529-533
02/15/2012
DOI: 10.1038/nature10825
PMCID: PMC3288636
PMID: 22343890
Abstract
Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord. Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and in most children at the time of recurrence. Affected children therefore are treated with radiation to the entire developing brain and spinal cord, followed by high-dose chemotherapy, with the ensuing deleterious effects on the developing nervous system. The mechanisms of dissemination through the cerebrospinal fluid are poorly studied, and medulloblastoma metastases have been assumed to be biologically similar to the primary tumour. Here we show that in both mouse and human medulloblastoma, the metastases from an individual are extremely similar to each other but are divergent from the matched primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted subclone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of metastatic medulloblastoma could be a major barrier to the development of effective targeted therapies.
Details
- Title: Subtitle
- Clonal selection drives genetic divergence of metastatic medulloblastoma
- Creators
- Xiaochong Wu - Arthur and Sonia Labatt Brain Tumour Research Center, Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, CanadaPaul A NorthcottAdrian DubucAdam J DupuyDavid J H ShihHendrik WittSidney CroulEric BouffetDaniel W FultsCharles G EberhartLivia GarziaTimothy Van MeterDavid ZagzagNada JabadoJeremy SchwartzentruberJacek MajewskiTodd E ScheetzStefan M PfisterAndrey KorshunovXiao-Nan Li - Baylor College of MedicineYoon-Jae ChoKeiko AkagiTobey J MacDonaldJan KosterMartin G McCabeAaron L SarverV Peter CollinsWilliam A WeissDavid A LargaespadaLara S CollierMichael D Taylor - Hospital for Sick ChildrenStephen W Scherer - University of Toronto
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.482(7386), pp.529-533
- DOI
- 10.1038/nature10825
- PMID
- 22343890
- PMCID
- PMC3288636
- NLM abbreviation
- Nature
- ISSN
- 1476-4687
- eISSN
- 1476-4687
- Publisher
- England
- Grant note
- Canadian Institutes of Health Research R01CA148699 / NCI NIH HHS K01CA122183 / NCI NIH HHS K01 CA122183 / NCI NIH HHS R01 CA148699 / NCI NIH HHS R01 CA148699-03 / NCI NIH HHS R01 CA113636 / NCI NIH HHS R56 NS055089 / NINDS NIH HHS R01 CA108622 / NCI NIH HHS R01 NS055089 / NINDS NIH HHS NS055089 / NINDS NIH HHS
- Language
- English
- Date published
- 02/15/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Anatomy and Cell Biology; Pathology; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980065102771
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