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

Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

Paper Id
COSP30160
Authors
Biankin AV,Waddell N,Kassahn KS,Gingras MC,Muthuswamy LB,Johns AL,Miller DK,Wilson PJ,Patch AM,Wu J,Chang DK,Cowley MJ,Gardiner BB,Song S,Harliwong I,Idrisoglu S,Nourse C,Nourbakhsh E,Manning S,Wani S,Gongora M,Pajic M,Scarlett CJ,Gill AJ,Pinho AV,Rooman I,Anderson M,Holmes O,Leonard C,Taylor D,Wood S,Xu Q,Nones K,Fink JL,Christ A,Bruxner T,Cloonan N,Kolle G,Newell F,Pinese M,Mead RS,Humphris JL,Kaplan W,Jones MD,Colvin EK,Nagrial AM,Humphrey ES,Chou A,Chin VT,Chantrill LA,Mawson A,Samra JS,Kench JG,Lovell JA,Daly RJ,Merrett ND,Toon C,Epari K,Nguyen NQ,Barbour A,Zeps N,Australian Pancreatic Cancer Genome Initiative,Kakkar N,Zhao F,Wu YQ,Wang M,Muzny DM,Fisher WE,Brunicardi FC,Hodges SE,Reid JG,Drummond J,Chang K,Han Y,Lewis LR,Dinh H,Buhay CJ,Beck T,Timms L,Sam M,Begley K,Brown A,Pai D,Panchal A,Buchner N,De Borja R,Denroche RE,Yung CK,Serra S,Onetto N,Mukhopadhyay D,Tsao MS,Shaw PA,Petersen GM,Gallinger S,Hruban RH,Maitra A,Iacobuzio-Donahue CA,Schulick RD,Wolfgang CL,Morgan RA,Lawlor RT,Capelli P,Corbo V,Scardoni M,Tortora G,Tempero MA,Mann KM,Jenkins NA,Perez-Mancera PA,Adams DJ,Largaespada DA,Wessels LF,Rust AG,Stein LD,Tuveson DA,Copeland NG,Musgrove EA,Scarpa A,Eshleman JR,Hudson TJ,Sutherland RL,Wheeler DA,Pearson JV,McPherson JD,Gibbs RA and Grimmond SM
Affiliation
The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia.
Journal
Nature 2012;491(7424):399-405
ISSN:1476-4687
PUBMED:23103869
Abstract
Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.
Paper Status
Curated
Genes Analysed
2524
Mutated Samples
99
Total No. of Samples
99
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 copy number variation data for this study. Only variants (classified as gain or loss) are listed. [more details]
CNV Gene Sample Position Minor Allele Copy Number Average Ploidy

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

2. For TCGA samples, Ascat algorithm is used to calculate the average ploidy.

3. For CGP samples, Picnic algorithm is used to calculate the average ploidy.

Type
This tab shows a table of count of samples having gain or loss for all genes [more details]
Gene Gain Samples Loss Samples Samples 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