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Reference

Intraclonal heterogeneity and distinct molecular mechanisms characterize the development of t(4;14) and t(11;14) myeloma.

Paper Id
COSP28746
Authors
Walker BA,Wardell CP,Melchor L,Hulkki S,Potter NE,Johnson DC,Fenwick K,Kozarewa I,Gonzalez D,Lord CJ,Ashworth A,Davies FE and Morgan GJ
Affiliation
Haemato-Oncology Research Unit, Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom;
Journal
Blood 2012
ISSN:1528-0020
PUBMED:22573403
Abstract
We have used whole exome sequencing to compare a group of presentation t(4;14) with t(11;14) cases of myeloma in order to define the mutational landscape. Each case was characterized by a median of 24.5 exonic non-synonymous SNVs and there was a consistently higher number of mutations in the t(4;14) group, but this did not reach statistical significance. We show that the transition/transversion rate in the two subgroups is similar suggesting that there was no specific mechanism leading to mutation differentiating the two groups. Only 3% of mutations were seen in both groups and recurrently mutated genes include NRAS, KRAS, BRAF and DIS3 as well as DNAH5, a member of the axonemal dynein family. The pattern of mutation in each group was distinct with the t(4;14) group being characterized by deregulation of chromatin organization, actin filament and microfilament movement. Recurrent RAS pathway mutations identified subclonal heterogeneity at a mutational level in both groups with mutations being present as either dominant or minor subclones. The presence of subclonal diversity was confirmed at a single cell level using other tumor acquired mutations. These results are consistent with a distinct molecular pathogenesis underlying each subgroup and have important impacts on targeted treatment strategies. The MRC Myeloma IX trial is registered at http://isrctn.org under ISRCTN68454111.
Paper Status
Curated
Genes Analysed
1007
Mutated Samples
22
Total No. of Samples
22
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Genes Samples CDS Mutation AA Mutation
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Non-Mutant Genes Gene Id (COSG)
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Non-Mutant Samples Sample Id (COSS)
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Sample Name Mutation Count
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Sample ID Sample Name ID NCV Annotation Zygosity Chromosome Genome start Genome stop Genome version Strand WT seq Mut seq
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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.

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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 the fusion mutations observed in this sample [more details]
Gene Sample Name Id Sample(COSS) CDS Mutation Somatic status Zygosity Validated Type