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Series GSE61502 Query DataSets for GSE61502
Status Public on Feb 27, 2015
Title Whole Genome Sequencing Informs Therapeutic Selection for Pancreatic Cancer
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole genome sequencing and CNV analysis of 100 pancreatic ductal adenocarcinomas. Chromosomal rearrangements leading to gene disruption were frequent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A, ROBO2) and novel candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation classified PDAC into 4 subtypes with potential clinical utility: stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3, and PIK3CA), but at low individual frequency. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2, PALB2 or RPA1), and a mutational signature of DNA damage repair deficiency. This subgroup was associated with response to platinum-based therapy and defines candidate biomarkers of therapeutic responsiveness.
 
Overall design DNA was assayed using Illumina SNP BeadChips as per manufacturer’s instructions (Illumina, San Diego CA) (HumanOmni1-Quad or HumanOmni2.5-8 BeadChips). SNP arrays were scanned and data was processed using the Genotyping module (v1.8.4) in Genomestudio v2010.3 (Illumina, San Diego CA) to calculate B-allele frequencies (BAF) and logR values. GenoCN4 and GAP5 were used to call somatic regions of copy number change – gain, loss or copy neutral LOH. Recurrent regions of copy number change were determined and genes within these regions were extracted using ENSEMBL v70 annotations. Significant regions of gain and loss were identified by GISTIC6.
 
Contributor(s) Waddell N, Pajic M, Patch A, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn M, Robertson A, Fudlullah M, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson M, Fink JL, Holmes O, Kazakoff S, Leonard C, Newell F, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Scarlett CJ, Pinho AV, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour AP, Zeps N, Jamieson NB, Graham JS, Grützmann R, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Sutherland RL, Pearson JV, Biankin AV, Grimmond SM
Citation(s) 25719666
Submission date Sep 17, 2014
Last update date Sep 04, 2015
Contact name Katia Nones
E-mail(s) katia.nones@qimrberghofer.edu.au
Phone +61 7 3845 3983
Organization name QIMR Berghofer MEdical Research Institute
Street address 300 Herston Road
City Brisbane
State/province QLD
ZIP/Postal code 4029
Country Australia
 
Platforms (2)
GPL8882 Illumina HumanOmni1-Quad BeadChip
GPL16104 Illumina HumanOmni2.5-8 BeadChip
Samples (100)
GSM1506648 Pancreatic carcinoma ICGC_0002
GSM1506649 Pancreatic carcinoma ICGC_0069
GSM1506650 Pancreatic carcinoma ICGC_0004
Relations
BioProject PRJNA261329

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE61502_RAW.tar 10.9 Gb (http)(custom) TAR (of IDAT, TXT)
Processed data provided as supplementary file

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