DOI: 10.1038/nature14169

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Whole genomes redefine the mutational landscape of pancreatic cancer

Nicola Waddell,Marina Pajic,Ann‐Marie Patch,David K. Chang,Karin S. Kassahn,Peter J. Bailey,Amber Johns,David Miller,Kátia Nones,Kelly Quek,Michael C. Quinn,Alan J. Robertson,Muhammad Zaki Hidayatullah Fadlullah,Tim Bruxner,Angelika N. Christ,Ivon Harliwong,Senel Idrisoglu,Suzanne Manning,Craig Nourse,Ehsan Nourbakhsh,Shivangi Wani,Peter J. Wilson,Emma Markham,Nicole Cloonan,Matthew Anderson,J. Lynn Fink,Oliver Holmes,Stephen H. Kazakoff,Conrad Leonard,Felicity Newell,Barsha Poudel,Sarah Song,Darrin Taylor,Nick M. Waddell,Scott Wood,Qinying Xu,Jianmin Wu,Mark Pinese,Mark J. Cowley,Hong C. Lee,Marc D. Jones,Adnan Nagrial,Jeremy L. Humphris,Lorraine A. Chantrill,Venessa Chin,Angela Steinmann,Amanda Mawson,Emily S. Humphrey,Emily K. Colvin,Angela Chou,Christopher J. Scarlett,Andreia V. Pinho,Marc Giry-Laterrière,Ilse Rooman,Jaswinder S. Samra,James G. Kench,Jessica A. Pettitt,Neil D. Merrett,Christopher W. Toon,Krishna Epari,Nam Q. Nguyen,Andrew P. Barbour,Nikolajs Zeps,Nigel B. Jamieson,Janet Graham,Simone P. Niclou,Rolf Bjerkvig,Robert Grützmann,Daniela E. Aust,Ralph H. Hruban,Anirban Maitra,Christine A. Iacobuzio-Donahue,Christopher L. Wolfgang,Richard A. Morgan,Rita T. Lawlor,Vincenzo Corbo,Claudio Bassi,Massimo Falconi,Giuseppe Zamboni,Giampaolo Tortora,Margaret A. Tempero,Anthony J. Gill,James R. Eshleman,Christian Pilarsky,Aldo Scarpa,Elizabeth A. Musgrove,John V. Pearson,Andrew V. Biankin,Sean M. Grimmond

CDKN2A

Genome instability

Pancreatic cancer

2015

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.

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“Whole genomes redefine the mutational landscape of pancreatic cancer” is a paper by Nicola Waddell Marina Pajic Ann‐Marie Patch David K. Chang Karin S. Kassahn Peter J. Bailey Amber Johns David Miller Kátia Nones Kelly Quek Michael C. Quinn Alan J. Robertson Muhammad Zaki Hidayatullah Fadlullah Tim Bruxner Angelika N. Christ Ivon Harliwong Senel Idrisoglu Suzanne Manning Craig Nourse Ehsan Nourbakhsh Shivangi Wani Peter J. Wilson Emma Markham Nicole Cloonan Matthew Anderson J. Lynn Fink Oliver Holmes Stephen H. Kazakoff Conrad Leonard Felicity Newell Barsha Poudel Sarah Song Darrin Taylor Nick M. Waddell Scott Wood Qinying Xu Jianmin Wu Mark Pinese Mark J. Cowley Hong C. Lee Marc D. Jones Adnan Nagrial Jeremy L. Humphris Lorraine A. Chantrill Venessa Chin Angela Steinmann Amanda Mawson Emily S. Humphrey Emily K. Colvin Angela Chou Christopher J. Scarlett Andreia V. Pinho Marc Giry-Laterrière Ilse Rooman Jaswinder S. Samra James G. Kench Jessica A. Pettitt Neil D. Merrett Christopher W. Toon Krishna Epari Nam Q. Nguyen Andrew P. Barbour Nikolajs Zeps Nigel B. Jamieson Janet Graham Simone P. Niclou Rolf Bjerkvig Robert Grützmann Daniela E. Aust Ralph H. Hruban Anirban Maitra Christine A. Iacobuzio-Donahue Christopher L. Wolfgang Richard A. Morgan Rita T. Lawlor Vincenzo Corbo Claudio Bassi Massimo Falconi Giuseppe Zamboni Giampaolo Tortora Margaret A. Tempero Anthony J. Gill James R. Eshleman Christian Pilarsky Aldo Scarpa Elizabeth A. Musgrove John V. Pearson Andrew V. Biankin Sean M. Grimmond published in 2015. It has an Open Access status of “green”. You can read and download a PDF Full Text of this paper here.