Journal article

Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

Andrew V Biankin, Nicola Waddell, Karin S Kassahn, Marie-Claude Gingras, Lakshmi B Muthuswamy, Amber L Johns, David K Miller, Peter J Wilson, Ann-Marie Patch, Jianmin Wu, David K Chang, Mark J Cowley, Brooke B Gardiner, Sarah Song, Ivon Harliwong, Senel Idrisoglu, Craig Nourse, Ehsan Nourbakhsh, Suzanne Manning, Shivangi Wani Show all



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) a..

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Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by Cancer Council NSW

Awarded by Cancer Institute NSW

Awarded by HGSC-BCM: NHGRI

Awarded by CPRIT

Awarded by Pancreatic Cancer Genetic Epidemiology Consortium, NIH

Awarded by Italian Ministry of University, Rome, Italy

Awarded by NIH

Awarded by NCI

Awarded by NIH SPORE grant

Awarded by AIRC (Associazione Italiana Ricerca sul Cancro), Italy

Awarded by Cancer Research UK



Funding Acknowledgements

This paper is dedicated to Robert L. Sutherland who died on 10 October 2012 of pancreatic cancer. We would like to thank C. Axford, D. Gwynne, M.-A. Brancato, S. Rowe, M. Thomas, S. Simpson and G. Hammond for central coordination of the Australian Pancreatic Cancer Genome Initiative, data management and quality control; M. Martyn-Smith, L. Braatvedt, H. Tang, V. Papangelis and M. Beilin for biospecimen acquisition; and W. Waterson, J. Shepperd, E. Campbell and E. Glasov for their efforts at the Queensland Centre for Medical Genomics. We also thank M. B. Hodgin, M. Debeljak and D. Trusty for technical assistance at Johns Hopkins University, and J. Lau, M. Karaus, K. Rabe, L. Zhang and T. Smyrk at the Mayo Clinic. We acknowledge the following funding support: National Health and Medical Research Council of Australia (NHMRC; 631701, 535903, 427601, 535914); Australian Government: Department of Innovation, Industry, Science, Research and Tertiary Education (DIISRTE); Australian Cancer Research Foundation (ACRF); Queensland Government (NIRAP); University of Queensland; Cancer Council NSW (SRP06-01; ICGC09-01; SRP11-01); Cancer Institute NSW (06/ECF/1-24, 09/CDF/2-40, 07/CDF/1-03, 10/CRF/1-01, 08/RSA/1-15, 07/CDF/1-28, 10/CDF/2-26, 10/FRL/2-03, 06/RSA/1-05, 09/RIG/1-02, 10/TPG/1-04, 11/REG/1-10, 11/CDF/3-26); Garvan Institute of Medical Research; Avner Nahmani Pancreatic Cancer Research Foundation; R.T. Hall Trust; Petre Foundation; Jane Hemstritch in memory of Philip Hemstritch; Gastroenterological Society of Australia (GESA); American Association for Cancer Research (AACR) Landon Foundation-INNOVATOR Award; Royal Australasian College of Surgeons (RACS); Royal Australasian College of Physicians (RACP); Royal College of Pathologists of Australasia (RCPA); HGSC-BCM: NHGRI U54 HG003273; CPRIT grant RP101353-P7 (Tumor Banking for Genomic Research and Clinical Translation Site 1); The Ontario Institute for Cancer Research; The Ontario Ministry of Economic Development and Innovation; Canada Foundation for Innovation; Pancreatic Cancer Genetic Epidemiology Consortium, NIH grant R01 CA97075; The Agency for Science, Technology, and Research (Singapore); University of Verona and Italian Ministry of University (FIRB RBAP10AHJB), Rome, Italy; Cancer Research UK; Wellcome Trust; CPRIT (Cancer Prevention Research Institute of Texas); NIH P50CA062924 (SPORE) and P01CA134292 (PPG); The Sol Goldman Pancreatic Cancer Research Center; NCI grant P50 CA102701 (Mayo Clinic SPORE in Pancreatic Cancer) and NCI grant R01 CA97075 (Pancreatic Cancer Genetic Epidemiology Consortium); NIH SPORE grant 2P50CA101955 (UMN/UAB), and AIRC (Associazione Italiana Ricerca sul Cancro) 5xmille grant 12182, Italy.