Subgroup-specific structural variation across 1,000 medulloblastoma genomes
| Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
|---|---|
| Data(s) |
29/10/2013
29/10/2013
2012
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| Resumo |
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 4 alpha. 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-beta signalling in Group 3, and NF-kappa B signalling in Group 4, suggest future avenues for rational, targeted therapy. CIHR Clinician-Scientist Phase II award CIHR ClinicianScientist Phase II award Sontag Foundation Sontag Foundation Pediatric Brain Tumour Foundation Pediatric Brain Tumour Foundation National Institutes of Health [CA159859] National Institutes of Health The Family of Kathleen Lorette The Family of Kathleen Lorette Clark H. Smith Brain Tumour Centre Clark H. Smith Brain Tumour Centre Montreal Childrens Hospital Foundation Montreal Children's Hospital Foundation Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre Chief of Research Fund Chief of Research Fund Cancer Genetics Program Cancer Genetics Program Garron Family Cancer Centre Garron Family Cancer Centre B.R.A.I.N. Child B.R.A.I.N. Child CIHR [ATE-110814] CIHR University of Toronto McLaughlin Centre University of Toronto McLaughlin Centre CIHR Institute of Cancer Research [AT1-112286] CIHR Institute of Cancer Research BC Cancer Foundation BC Cancer Foundation Children's Discovery Institute Childrens Discovery Institute Restracomp Fellowship (Hospital for Sick Children) Restracomp Fellowship (Hospital for Sick Children) Ontario Institute for Cancer Research Ontario Institute for Cancer Research Government of Ontario Government of Ontario NIH NIH [CA86335, CA116804, CA138292] NCI NCI [28XS100, 29XS193] Southeastern Brain Tumour Foundation Southeastern Brain Tumour Foundation Brain Tumour Foundation for Children Brain Tumour Foundation for Children UK Children's Cancer and Leukaemia Group (CCLG) [BS-2007-04] UK Childrens Cancer and Leukaemia Group (CCLG) German Cancer Aid German Cancer Aid [109252] |
| Identificador |
NATURE, LONDON, v. 488, n. 7409, supl. 4, Part 1-2, pp. 49-56, AUG 2, 2012 0028-0836 http://www.producao.usp.br/handle/BDPI/36147 10.1038/nature11327 |
| Idioma(s) |
eng |
| Publicador |
NATURE PUBLISHING GROUP LONDON |
| Relação |
NATURE |
| Direitos |
restrictedAccess Copyright NATURE PUBLISHING GROUP |
| Palavras-Chave | #HEDGEHOG PATHWAY INHIBITOR #COPY-NUMBER ALTERATION #PARKINSONS-DISEASE #ALPHA-SYNUCLEIN #HUMAN CANCERS #BETA FAMILY #SYNPHILIN-1 #PROTEIN #MYC #CHILDHOOD #MULTIDISCIPLINARY SCIENCES |
| Tipo |
article original article publishedVersion |
