This tab shows an overview of the selected study/paper [more details]
Reference

Dissecting the genomic complexity underlying medulloblastoma.

Paper Id
COSP29353
Authors
Jones DT,Jäger N,Kool M,Zichner T,Hutter B,Sultan M,Cho YJ,Pugh TJ,Hovestadt V,Stütz AM,Rausch T,Warnatz HJ,Ryzhova M,Bender S,Sturm D,Pleier S,Cin H,Pfaff E,Sieber L,Wittmann A,Remke M,Witt H,Hutter S,Tzaridis T,Weischenfeldt J,Raeder B,Avci M,Amstislavskiy V,Zapatka M,Weber UD,Wang Q,Lasitschka B,Bartholomae CC,Schmidt M,von Kalle C,Ast V,Lawerenz C,Eils J,Kabbe R,Benes V,van Sluis P,Koster J,Volckmann R,Shih D,Betts MJ,Russell RB,Coco S,Tonini GP,Schüller U,Hans V,Graf N,Kim YJ,Monoranu C,Roggendorf W,Unterberg A,Herold-Mende C,Milde T,Kulozik AE,von Deimling A,Witt O,Maass E,Rössler J,Ebinger M,Schuhmann MU,Frühwald MC,Hasselblatt M,Jabado N,Rutkowski S,von Bueren AO,Williamson D,Clifford SC,McCabe MG,Collins VP,Wolf S,Wiemann S,Lehrach H,Brors B,Scheurlen W,Felsberg J,Reifenberger G,Northcott PA,Taylor MD,Meyerson M,Pomeroy SL,Yaspo ML,Korbel JO,Korshunov A,Eils R,Pfister SM and Lichter P
Affiliation
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Journal
Nature 2012;488(7409):100-5
ISSN:1476-4687
PUBMED:22832583
Abstract
Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients.
Paper Status
Curated
Genes Analysed
982
Mutated Samples
114
Total No. of Samples
115
This tab shows genes with mutations in the selected study/paper [more details]
Genes Samples CDS Mutation AA Mutation
This tab shows genes without mutations in the selected study/paper [more details]
Non-Mutant Genes Gene Id (COSG)
This tab shows samples without mutations in the selected study/paper [more details]
Non-Mutant Samples Sample Id (COSS)
This tab shows mutated samples in the selected study/paper [more details]
Sample Name Mutation Count
This tab shows non coding variant in the selected study/paper [more details]
Sample ID Sample Name ID NCV Annotation Zygosity Chromosome Genome start Genome stop Genome version Strand WT seq Mut seq
This tab shows the gene expression and copy number variation data for this study. [more details]

Table Information

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The table currently shows only high value (numeric) copy number data. Copy number segments are excluded if the total copy number and minor allele values are unknown.

Click here to include all copy number data. For more detailed information about copy number data and gain/loss definitions click here.

Sample Gene Expression Expr Level (Z-Score)

Over Expressed; Z-Score > 2.0

Under Expressed; Z-Score < -2.0

Normal; Z-Score within the range -2.0 to 2.0

CN Type Minor Allele Copy Number CN Segment Posn. Average Ploidy

1. N/A represents cases where the average ploidy value is not available( mostly ICGC samples). For some TCGA samples where the minor allele information is not available the average ploidy value could not be calculated.

2. For TCGA samples, the ASCAT algorithm was used to calculate the average ploidy.

3. For CGP samples, the PICNIC algorithm was used to calculate the average ploidy.

CNV
This tab shows a summary table with counts (number of samples) for CNV gain/loss and under/over expression for all genes. [more details]

The results shown in this table are derived from all copy number data. This includes non-numeric data with descriptive definitions of gain/loss.

  Copy Number Expression
Gene Gain Loss Tested Over Under Tested
This tab shows the fusion mutations observed in this sample [more details]
Gene Sample Name Id Sample(COSS) CDS Mutation Somatic status Zygosity Validated Type