Whole genomes redefine the mutational landscape of pancreatic cancer

Xu, Qinying; Yeung, Shinn; Xu, Q.; Zeps, Nikolajs; Zamboni, Giuseppe; Xu, Christina; Wood, Scott; Watson, Clare; Wong, Rachel; Pajic, Marina; Wood, David; Patch, Ann-Marie; Worthley, Chris; Waddell, Nick; Wood, S.; Rowe, Sarah J.; Simpson, Skye H.; Thomas, Michelle T.; Quinn, Michael C. J.; Scott Mead, R.; Kassahn, Karin S.; Am, Patch; Pettit, Jessica; Tao, Jiang; Sutherland, Robert L.; Johns, Amber L.; Pavlakis, Nick; Pavey, Darren; Nq, Nguyen; Nones, Katia; O’Connnor, Chelsie; Miller, David; Bailey, Peter; Quek, Kelly; Robertson, Alan J.; Pleass, Henry C.; Richardson, Arthur; Wilson, Peter J.; Fadlullah, Muhammad Z. H.; Dk, Chang; Sandroussi, Charbel; Texler, Michael; Sp, Niclou; Christ, Angelika N.; Spry, Nigel A.; Ks, Kassahn; Rh, Hruban; Ruszkiewicz, Andrew R.; Pj, Wilson; Chang, David K.; Tan, Chuan P.; Ra, Morgan; Papangelis, Virginia; Tang, Henry; Nourse, Craig; Harliwong, Ivon; Rt, Lawlor; O’Rourke, Thomas J.; Idrisoglu, Senel; Nourbakhsh, Ehsan; Wani, Shivangi; Slater, Kellee; Manning, Suzanne; Sh, Kazakoff; Schulick, Richard D.; Scardoni, Maria; Fink, J. Lynn; Oien, Karen; Bruxner, Tim J. C.; Kazakoff, Stephen H.; Markham, Emma; Martyn-Smith, Mona; Humphris, Jeremy L.; Cloonan, Nicole; Mc, Quinn; Tj, Bruxner; Steinmann, Angela M.; Anderson, Matthew J.; Al, Johns; DiPietro, Renee; Cowley, Mark J.; Daly, Roger J.; Mj, Anderson; Lee, Hong C.; Holmes, Oliver; Lynn Fink, J.; Waddell, Nicola; Jl, Fink; Jones, Marc D.; Poudel, Barsha; Scarlett, Christopher J.; Miller, David K.; Pinho, Andreia V.; Song, Sarah; Nagrial, Adnan M.; Leonard, Conrad; Gongora, Milena; Mz, Fadlullah; Ek, Colvin; Taylor, Darrin; Newell, Felicity; Rooman, Ilse; Samra, Jaswinder S.; Js, Samra; Nagaraj, Shivashankar; Jg, Kench; Pettitt, Jessica A.; Wu, Jianmin; Krisnan, Keerthana; Humphrey, Emily S.; Toon, Christopher; Ja, Pettitt; Guminski, Alex; Pinese, Mark; Nd, Merrett; Das, Amitabha; Cosman, Peter H.; Ismail, Kasim; Mj, Cowley; Giry-Laterriere, Marc; Lam Duncan McLeod, Vincent W.; Hc, Lee; Chantrill, Lorraine A.; James, Virginia; Cooper, Caroline L.; Md, Jones; Wolfgang, Christopher L.; An, Christ; Joseph, David; Kench, James G.; Nb, Jamieson; Crawford, Michael; Merrett, Neil D.; Gallagher, James; Js, Graham; La, Chantrill; Epari, Krishna; Forest, Cindy; Humphris, Jeremy; Laycock, Andrew; Nguyen, Nam Q.; Epari, Krishna P.; Sm, Grimmond; Fletcher, David R.; Jamieson, Nigel B.; Mukhedkar, Sanjay; Es, Humphrey; Graham, Janet S.; DeBoer, Bastiaan; Niclou, Simone P.; Mawson, Amanda; Feeney, Kynan; Nguyen, Nan Q.; Tortora, Giampaolo; Cl, Wolfgang; Grützmann, Robert; Chin, Venessa; Cj, Scarlett; Tempero, Margaret A.; Debrencini, Tamara; Barbour, Andrew; Colvin, Emily K.; Hruban, Ralph H.; Clouston, Andrew D.; Maitra, Anirban; Martin, Patrick; Pilarsky, Christian; Fawcett, Jonathan W.; Iacobuzio-Donahue, Christine A.; Hatzifotis, Michael; Scarpa, Aldo; Hodgkinson, Peter; Bjerkvig, Rolf; Christophi, Christopher; Chou, Angela; Morgan, Richard A.; Ma, Tempero; Pearson, John V.; Aust, Daniela; Mountain, Angela; Lawlor, Rita T.; Aj, Robertson; Corbo, Vincenzo; Jr, Eshleman; Hodgin, Mary; Ea, Musgrove; Falconi, Massimo; Am, Nagrial; Jv, Pearson; Hair, Jane; Chin, Venessa T.; Nikfarjam, Mehrdad; Initiative, Australian Pancreatic Cancer Genome; Bassi, Claudio; Gill, Anthony J.; Ching Lee, Hong; Am, Steinmann; Eshleman, James R.; Brancato, Mary-Anne L.; Av, Pinho; Asghari, Ray; Musgrove, Elizabeth A.; Ballal, Mo; Chai, Ming; Beilin, Maria; Ca, Iacobuzio Donahue; Chen, John; Brooke-Smith, Mark E.; Grimmond, Sean M.; Barbour, Andrew P.; Chiang, Amy; Aj, Gill; Beghelli, Stefania; Biankin, Andrew V.; Av, Biankin

Dissemin
Marina Pajic
Xu et al., 2015

Published in

Nature Research, Nature, 7540(518), p. 495-501, 2015

DOI: 10.1038/nature14169

Tools

Export citation

Format

@article{Xu2015,
  abstract = {Published online 25 February 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. ; Nicola Waddell . Karin S. Kassahn . Nam Q. Nguyen . et al. (Australian Pancreatic Cancer Genome Initiative)},
  author = {Xu, Qinying and Yeung, Shinn and Xu, Q. and Zeps, Nikolajs and Zamboni, Giuseppe and Xu, Christina and Wood, Scott and Watson, Clare and Wong, Rachel and Pajic, Marina and Wood, David and Patch, Ann-Marie and Worthley, Chris and Waddell, Nick and Wood, S. and Rowe, Sarah J. and Simpson, Skye H. and Thomas, Michelle T. and Quinn, Michael C. J. and Scott Mead, R. and Kassahn, Karin S. and Am, Patch and Pettit, Jessica and Tao, Jiang and Sutherland, Robert L. and Johns, Amber L. and Pavlakis, Nick and Pavey, Darren and Nq, Nguyen and Nones, Katia and O’Connnor, Chelsie and Miller, David and Bailey, Peter and Quek, Kelly and Robertson, Alan J. and Pleass, Henry C. and Richardson, Arthur and Wilson, Peter J. and Fadlullah, Muhammad Z. H. and Dk, Chang and Sandroussi, Charbel and Texler, Michael and Sp, Niclou and Christ, Angelika N. and Spry, Nigel A. and Ks, Kassahn and Rh, Hruban and Ruszkiewicz, Andrew R. and Pj, Wilson and Chang, David K. and Tan, Chuan P. and Ra, Morgan and Papangelis, Virginia and Tang, Henry and Nourse, Craig and Harliwong, Ivon and Rt, Lawlor and O’Rourke, Thomas J. and Idrisoglu, Senel and Nourbakhsh, Ehsan and Wani, Shivangi and Slater, Kellee and Manning, Suzanne and Sh, Kazakoff and Schulick, Richard D. and Scardoni, Maria and Fink, J. Lynn and Oien, Karen and Bruxner, Tim J. C. and Kazakoff, Stephen H. and Markham, Emma and Martyn-Smith, Mona and Humphris, Jeremy L. and Cloonan, Nicole and Mc, Quinn and Tj, Bruxner and Steinmann, Angela M. and Anderson, Matthew J. and Al, Johns and DiPietro, Renee and Cowley, Mark J. and Daly, Roger J. and Mj, Anderson and Lee, Hong C. and Holmes, Oliver and Lynn Fink, J. and Waddell, Nicola and Jl, Fink and Jones, Marc D. and Poudel, Barsha and Scarlett, Christopher J. and Miller, David K. and Pinho, Andreia V. and Song, Sarah and Nagrial, Adnan M. and Leonard, Conrad and Gongora, Milena and Mz, Fadlullah and Ek, Colvin and Taylor, Darrin and Newell, Felicity and Rooman, Ilse and Samra, Jaswinder S. and Js, Samra and Nagaraj, Shivashankar and Jg, Kench and Pettitt, Jessica A. and Wu, Jianmin and Krisnan, Keerthana and Humphrey, Emily S. and Toon, Christopher and Ja, Pettitt and Guminski, Alex and Pinese, Mark and Nd, Merrett and Das, Amitabha and Cosman, Peter H. and Ismail, Kasim and Mj, Cowley and Giry-Laterriere, Marc and Lam Duncan McLeod, Vincent W. and Hc, Lee and Chantrill, Lorraine A. and James, Virginia and Cooper, Caroline L. and Md, Jones and Wolfgang, Christopher L. and An, Christ and Joseph, David and Kench, James G. and Nb, Jamieson and Crawford, Michael and Merrett, Neil D. and Gallagher, James and Js, Graham and La, Chantrill and Epari, Krishna and Forest, Cindy and Humphris, Jeremy and Laycock, Andrew and Nguyen, Nam Q. and Epari, Krishna P. and Sm, Grimmond and Fletcher, David R. and Jamieson, Nigel B. and Mukhedkar, Sanjay and Es, Humphrey and Graham, Janet S. and DeBoer, Bastiaan and Niclou, Simone P. and Mawson, Amanda and Feeney, Kynan and Nguyen, Nan Q. and Tortora, Giampaolo and Cl, Wolfgang and Grützmann, Robert and Chin, Venessa and Cj, Scarlett and Tempero, Margaret A. and Debrencini, Tamara and Barbour, Andrew and Colvin, Emily K. and Hruban, Ralph H. and Clouston, Andrew D. and Maitra, Anirban and Martin, Patrick and Pilarsky, Christian and Fawcett, Jonathan W. and Iacobuzio-Donahue, Christine A. and Hatzifotis, Michael and Scarpa, Aldo and Hodgkinson, Peter and Bjerkvig, Rolf and Christophi, Christopher and Chou, Angela and Morgan, Richard A. and Ma, Tempero and Pearson, John V. and Aust, Daniela and Mountain, Angela and Lawlor, Rita T. and Aj, Robertson and Corbo, Vincenzo and Jr, Eshleman and Hodgin, Mary and Ea, Musgrove and Falconi, Massimo and Am, Nagrial and Jv, Pearson and Hair, Jane and Chin, Venessa T. and Nikfarjam, Mehrdad and Initiative, Australian Pancreatic Cancer Genome and Bassi, Claudio and Gill, Anthony J. and Ching Lee, Hong and Am, Steinmann and Eshleman, James R. and Brancato, Mary-Anne L. and Av, Pinho and Asghari, Ray and Musgrove, Elizabeth A. and Ballal, Mo and Chai, Ming and Beilin, Maria and Ca, Iacobuzio Donahue and Chen, John and Brooke-Smith, Mark E. and Grimmond, Sean M. and Barbour, Andrew P. and Chiang, Amy and Aj, Gill and Beghelli, Stefania and Biankin, Andrew V. and Av, Biankin},
  doi = {10.1038/nature14169},
  journal = {Nature},
  month = {feb},
  pages = {495-501},
  title = {Whole genomes redefine the mutational landscape of pancreatic cancer},
  url = {http://www.nature.com/articles/nature14169.pdf},
  volume = {518},
  year = {2015}
}

Download

Export citation

Search in Google Scholar

Whole genomes redefine the mutational landscape of pancreatic cancer

Journal article published in 2015 by Qinying Xu, Shinn Yeung, Q. Xu, Nikolajs Zeps, Giuseppe Zamboni, Christina Xu, Scott Wood, Clare Watson, Rachel Wong, Marina Pajic

, David Wood, Ann-Marie Patch, Chris Worthley, Nick Waddell, S. Wood and other authors. Qinying Xu, Shinn Yeung, Q. Xu, Nikolajs Zeps, Giuseppe Zamboni, Christina Xu, Scott Wood, Clare Watson, Rachel Wong, Marina Pajic

, David Wood, Ann-Marie Patch, Chris Worthley, Nick Waddell, S. Wood, Sarah J. Rowe, Skye H. Simpson, Michelle T. Thomas, Michael C. J. Quinn, R. Scott Mead, Karin S. Kassahn, Patch Am, Jessica Pettit, Jiang Tao, Robert L. Sutherland, Amber L. Johns, Nick Pavlakis, Darren Pavey, Nguyen Nq, Katia Nones

, Chelsie O’Connnor, David Miller, Peter Bailey, Kelly Quek, Alan J. Robertson, Henry C. Pleass, Arthur Richardson, Peter J. Wilson, Muhammad Z. H. Fadlullah, Chang Dk, Charbel Sandroussi, Michael Texler, Niclou Sp, Angelika N. Christ, Nigel A. Spry, Kassahn Ks, Hruban Rh, Andrew R. Ruszkiewicz, Wilson Pj, David K. Chang, Chuan P. Tan, Morgan Ra, Virginia Papangelis, Henry Tang, Craig Nourse, Ivon Harliwong, Lawlor Rt, Thomas J. O’Rourke, Senel Idrisoglu, Ehsan Nourbakhsh, Shivangi Wani, Kellee Slater, Suzanne Manning, Kazakoff Sh, Richard D. Schulick, Maria Scardoni, J. Lynn Fink, Karen Oien, Tim J. C. Bruxner, Stephen H. Kazakoff, Emma Markham, Mona Martyn-Smith, Jeremy L. Humphris, Nicole Cloonan, Quinn Mc, Bruxner Tj, Angela M. Steinmann, Matthew J. Anderson, Johns Al, Renee DiPietro, Mark J. Cowley, Roger J. Daly, Anderson Mj, Hong C. Lee, Oliver Holmes, J. Lynn Fink, Nicola Waddell, Fink Jl, Marc D. Jones, Barsha Poudel, Christopher J. Scarlett, David K. Miller, Andreia V. Pinho, Sarah Song, Adnan M. Nagrial, Conrad Leonard, Milena Gongora, Fadlullah Mz, Colvin Ek, Darrin Taylor, Felicity Newell, Ilse Rooman, Jaswinder S. Samra, Samra Js, Shivashankar Nagaraj, Kench Jg, Jessica A. Pettitt, Jianmin Wu

, Keerthana Krisnan, Emily S. Humphrey, Christopher Toon, Pettitt Ja, Alex Guminski, Mark Pinese, Merrett Nd, Amitabha Das, Peter H. Cosman, Kasim Ismail, Cowley Mj, Marc Giry-Laterriere, Vincent W. Lam Duncan McLeod, Lee Hc, Lorraine A. Chantrill, Virginia James, Caroline L. Cooper, Jones Md, Christopher L. Wolfgang, Christ An, David Joseph, James G. Kench, Jamieson Nb, Michael Crawford, Neil D. Merrett, James Gallagher, Graham Js, Chantrill La, Krishna Epari, Cindy Forest, Jeremy Humphris, Andrew Laycock, Nam Q. Nguyen, Krishna P. Epari, Grimmond Sm, David R. Fletcher, Nigel B. Jamieson, Sanjay Mukhedkar, Humphrey Es, Janet S. Graham, Bastiaan DeBoer, Simone P. Niclou, Amanda Mawson, Kynan Feeney, Nan Q. Nguyen, Giampaolo Tortora, Wolfgang Cl, Robert Grützmann, Venessa Chin

, Scarlett Cj, Margaret A. Tempero, Tamara Debrencini, Andrew Barbour

, Emily K. Colvin, Ralph H. Hruban, Andrew D. Clouston, Anirban Maitra, Patrick Martin, Christian Pilarsky, Jonathan W. Fawcett, Christine A. Iacobuzio-Donahue, Michael Hatzifotis, Aldo Scarpa

, Peter Hodgkinson, Rolf Bjerkvig, Christopher Christophi, Angela Chou

, Richard A. Morgan, Tempero Ma, John V. Pearson, Daniela Aust, Angela Mountain, Rita T. Lawlor

, Robertson Aj, Vincenzo Corbo, Eshleman Jr, Mary Hodgin, Musgrove Ea, Massimo Falconi, Nagrial Am, Pearson Jv, Jane Hair, Venessa T. Chin, Mehrdad Nikfarjam

, Australian Pancreatic Cancer Genome Initiative, Claudio Bassi, Anthony J. Gill, Hong Ching Lee, Steinmann Am, James R. Eshleman, Mary-Anne L. Brancato, Pinho Av, Ray Asghari, Elizabeth A. Musgrove, Mo Ballal, Ming Chai, Maria Beilin, Iacobuzio Donahue Ca, John Chen, Mark E. Brooke-Smith, Sean M. Grimmond, Andrew P. Barbour, Amy Chiang, Gill Aj, Stefania Beghelli, Andrew V. Biankin, Biankin Av

Show less

This paper is made freely available by the publisher.

Full text: Download

Preprint: archiving allowed

Upload

Postprint: archiving restricted

Upload

Published version: archiving forbidden

Policy details

Data provided by

Abstract

Published online 25 February 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. ; Nicola Waddell . Karin S. Kassahn . Nam Q. Nguyen . et al. (Australian Pancreatic Cancer Genome Initiative)

Published in

Links

Tools

Whole genomes redefine the mutational landscape of pancreatic cancer

Abstract