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Statements

Subject Item
n2:RIV%2F65269705%3A_____%2F12%3A%230001635%21RIV13-MZ0-65269705
rdf:type
skos:Concept n9:Vysledek
dcterms:description
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.   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.  
dcterms:title
Subgroup-specific structural variation across 1,00 meduloblastoma genomes Subgroup-specific structural variation across 1,00 meduloblastoma genomes
skos:prefLabel
Subgroup-specific structural variation across 1,00 meduloblastoma genomes Subgroup-specific structural variation across 1,00 meduloblastoma genomes
skos:notation
RIV/65269705:_____/12:#0001635!RIV13-MZ0-65269705
n9:predkladatel
n10:ico%3A65269705
n4:aktivita
n8:V n8:I
n4:aktivity
I, V
n4:cisloPeriodika
7409
n4:dodaniDat
n18:2013
n4:domaciTvurceVysledku
n14:5658179 n14:7248857
n4:druhVysledku
n12:J
n4:duvernostUdaju
n6:S
n4:entitaPredkladatele
n17:predkladatel
n4:idSjednocenehoVysledku
172298
n4:idVysledku
RIV/65269705:_____/12:#0001635
n4:jazykVysledku
n11:eng
n4:klicovaSlova
brain tumour
n4:klicoveSlovo
n13:brain%20tumour
n4:kodStatuVydavatele
GB - Spojené království Velké Británie a Severního Irska
n4:kontrolniKodProRIV
[B08E504523AC]
n4:nazevZdroje
Nature
n4:obor
n7:FD
n4:pocetDomacichTvurcuVysledku
2
n4:pocetTvurcuVysledku
135
n4:rokUplatneniVysledku
n18:2012
n4:svazekPeriodika
488
n4:tvurceVysledku
Zitterbart, Karel Northcott, Paul A Křen, Leoš
n4:wos
000307010700030
s:issn
0028-0836
s:numberOfPages
8
n15:doi
10.1038/nature11327