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

Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer.

Paper Id
COSP29675
Authors
Peifer M,Fernández-Cuesta L,Sos ML,George J,Seidel D,Kasper LH,Plenker D,Leenders F,Sun R,Zander T,Menon R,Koker M,Dahmen I,Müller C,Di Cerbo V,Schildhaus HU,Altmüller J,Baessmann I,Becker C,de Wilde B,Vandesompele J,Böhm D,Ansén S,Gabler F,Wilkening I,Heynck S,Heuckmann JM,Lu X,Carter SL,Cibulskis K,Banerji S,Getz G,Park KS,Rauh D,Grütter C,Fischer M,Pasqualucci L,Wright G,Wainer Z,Russell P,Petersen I,Chen Y,Stoelben E,Ludwig C,Schnabel P,Hoffmann H,Muley T,Brockmann M,Engel-Riedel W,Muscarella LA,Fazio VM,Groen H,Timens W,Sietsma H,Thunnissen E,Smit E,Heideman DA,Snijders PJ,Cappuzzo F,Ligorio C,Damiani S,Field J,Solberg S,Brustugun OT,Lund-Iversen M,Sänger J,Clement JH,Soltermann A,Moch H,Weder W,Solomon B,Soria JC,Validire P,Besse B,Brambilla E,Brambilla C,Lantuejoul S,Lorimier P,Schneider PM,Hallek M,Pao W,Meyerson M,Sage J,Shendure J,Schneider R,Büttner R,Wolf J,Nürnberg P,Perner S,Heukamp LC,Brindle PK,Haas S and Thomas RK
Affiliation
1] Department of Translational Genomics, University of Cologne, Cologne, Germany. [2] Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. [3].
Journal
Nature genetics 2012
ISSN:1546-1718
PUBMED:22941188
Abstract
Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis. We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 ± 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated analyses of the various data sets to identify pathogenetically relevant mutated genes. In all cases, we found evidence for inactivation of TP53 and RB1 and identified recurrent mutations in the CREBBP, EP300 and MLL genes that encode histone modifiers. Furthermore, we observed mutations in PTEN, SLIT2 and EPHA7, as well as focal amplifications of the FGFR1 tyrosine kinase gene. Finally, we detected many of the alterations found in humans in SCLC tumors from Tp53 and Rb1 double knockout mice. Our study implicates histone modification as a major feature of SCLC, reveals potentially therapeutically tractable genomic alterations and provides a generalizable framework for the identification of biologically relevant genes in the context of high mutational background.
Paper Status
Curated
Genes Analysed
5975
Mutated Samples
42
Total No. of Samples
42
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