Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/102320
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Type: Journal article
Title: Whole genomes redefine the mutational landscape of pancreatic cancer
Author: Waddell, N.
Pajic, M.
Patch, A.
Chang, D.
Kassahn, K.
Bailey, P.
Johns, A.
Miller, D.
Nones, K.
Quek, K.
Quinn, M.
Robertson, A.
Fadlullah, M.
Bruxner, T.
Christ, A.
Harliwong, I.
Idrisoglu, S.
Manning, S.
Nourse, C.
Nourbakhsh, E.
et al.
Citation: Nature, 2015; 518(7540):495-501
Publisher: Nature Publishing Group
Issue Date: 2015
ISSN: 0028-0836
1476-4687
Statement of
Responsibility: 
Nicola Waddell ... Karin S. Kassahn ... Nam Q. Nguyen ... et al. (Australian Pancreatic Cancer Genome Initiative)
Abstract: Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed 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 patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.
Keywords: Australian Pancreatic Cancer Genome Initiative
Description: Published online 25 February 2015
Rights: ©2015 Macmillan Publishers Limited. All rights reserved
RMID: 0030035702
DOI: 10.1038/nature14169
Grant ID: http://purl.org/au-research/grants/nhmrc/631701
http://purl.org/au-research/grants/nhmrc/535903
http://purl.org/au-research/grants/nhmrc/427601
Appears in Collections:Medicine publications

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