Hypermutation in pancreatic cancer

Jeremy L. Humphris; Ann-Marie Patch; Katia Nones; Peter J. Bailey; Amber L. Johns; Skye McKay; David K. Chang; David K. Miller; Marina Pajic; Karin S. Kassahn; Michael C. J. Quinn; Timothy J. C. Bruxner; Angelika N. Christ; Ivon Harliwong; Senel Idrisoglu; Suzanne Manning; Craig Nourse; Ehsan Nourbakhsh; Andrew Stone; Peter J. Wilson; Matthew Anderson; J. Lynn Fink; Oliver Holmes; Stephen Kazakoff; Conrad Leonard; Felicity Newell; Nick Waddell; Scott Wood; Ronald S. Mead; Qinying Xu; Jianmin Wu; Mark Pinese; Mark J. Cowley; Marc D. Jones; Adnan M. Nagrial; Venessa T. Chin; Lorraine A. Chantrill; Amanda Mawson; Angela Chou; Christopher J. Scarlett; Andreia V. Pinho; Ilse Rooman; Marc Giry-Laterriere; Jaswinder S. Samra; James G. Kench; Neil D. Merrett; Christopher W. Toon; Krishna Epari; Nam Q. Nguyen; Andrew Barbour; Nikolajs Zeps; Nigel B. Jamieson; Colin J. McKay; C. Ross Carter; Euan J. Dickson; Janet S. Graham; Fraser Duthie; Karin Oien; Jane Hair; Jennifer P. Morton; Owen J. Sansom; Robert Grützmann; Ralph H. Hruban; Anirban Maitra; Christine A. Iacobuzio-Donahue; Richard D. Schulick; Christopher L. Wolfgang; Richard A. Morgan; Rita T. Lawlor; Borislav Rusev; Vincenzo Corbo; Roberto Salvia; Ivana Cataldo; Giampaolo Tortora; Margaret A. Tempero; null Australian Pancreatic Cancer Genome Initiative; Oliver Hofmann; James R. Eshleman; Christian Pilarsky; Aldo Scarpa; Elizabeth A. Musgrove; Anthony J. Gill; John V. Pearson; Sean M. Grimmond; Nicola Waddell; Andrew V. Biankin

doi:10.1053/j.gastro.2016.09.060

Hypermutation in pancreatic cancer

Jeremy L. Humphris, Ann-Marie Patch, Katia Nones, Peter J. Bailey, Amber L. Johns, Skye McKay, David K. Chang, David K. Miller, Marina Pajic, Karin S. Kassahn, Michael C. J. Quinn, Timothy J. C. Bruxner, Angelika N. Christ, Ivon Harliwong, Senel Idrisoglu, Suzanne Manning, Craig Nourse, Ehsan Nourbakhsh, Andrew Stone, Peter J. WilsonMatthew Anderson, J. Lynn Fink, Oliver Holmes, Stephen Kazakoff, Conrad Leonard, Felicity Newell, Nick Waddell, Scott Wood, Ronald S. Mead, Qinying Xu, Jianmin Wu, Mark Pinese, Mark J. Cowley, Marc D. Jones, Adnan M. Nagrial, Venessa T. Chin, Lorraine A. Chantrill, Amanda Mawson, Angela Chou, Christopher J. Scarlett, Andreia V. Pinho, Ilse Rooman, Marc Giry-Laterriere, Jaswinder S. Samra, James G. Kench, Neil D. Merrett, Christopher W. Toon, Krishna Epari, Nam Q. Nguyen, Andrew Barbour, Nikolajs Zeps, Nigel B. Jamieson, Colin J. McKay, C. Ross Carter, Euan J. Dickson, Janet S. Graham, Fraser Duthie, Karin Oien, Jane Hair, Jennifer P. Morton, Owen J. Sansom, Robert Grützmann, Ralph H. Hruban, Anirban Maitra, Christine A. Iacobuzio-Donahue, Richard D. Schulick, Christopher L. Wolfgang, Richard A. Morgan, Rita T. Lawlor, Borislav Rusev, Vincenzo Corbo, Roberto Salvia, Ivana Cataldo, Giampaolo Tortora, Margaret A. Tempero, Australian Pancreatic Cancer Genome Initiative, Oliver Hofmann, James R. Eshleman, Christian Pilarsky, Aldo Scarpa, Elizabeth A. Musgrove, Anthony J. Gill, John V. Pearson, Sean M. Grimmond, Nicola Waddell, Andrew V. Biankin

Western Sydney University

Research output: Contribution to journal › Article › peer-review

175 Citations (Scopus)

Abstract

Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

Original language	English
Pages (from-to)	68-74
Number of pages	9
Journal	Gastroenterology
Volume	152
Issue number	1
DOIs	https://doi.org/10.1053/j.gastro.2016.09.060
Publication status	Published - 2017

Keywords

cancer
cancer genetics
pancreas

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1053/j.gastro.2016.09.060

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Humphris, J. L., Patch, A.-M., Nones, K., Bailey, P. J., Johns, A. L., McKay, S., Chang, D. K., Miller, D. K., Pajic, M., Kassahn, K. S., Quinn, M. C. J., Bruxner, T. J. C., Christ, A. N., Harliwong, I., Idrisoglu, S., Manning, S., Nourse, C., Nourbakhsh, E., Stone, A., ... Biankin, A. V. (2017). Hypermutation in pancreatic cancer. Gastroenterology, 152(1), 68-74. https://doi.org/10.1053/j.gastro.2016.09.060

@article{83a8c4719eb846df97a5f3791962a314,

title = "Hypermutation in pancreatic cancer",

abstract = "Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.",

keywords = "cancer, cancer genetics, pancreas",

author = "Humphris, {Jeremy L.} and Ann-Marie Patch and Katia Nones and Bailey, {Peter J.} and Johns, {Amber L.} and Skye McKay and Chang, {David K.} and Miller, {David K.} and Marina Pajic and Kassahn, {Karin S.} and Quinn, {Michael C. J.} and Bruxner, {Timothy J. C.} and Christ, {Angelika N.} and Ivon Harliwong and Senel Idrisoglu and Suzanne Manning and Craig Nourse and Ehsan Nourbakhsh and Andrew Stone and Wilson, {Peter J.} and Matthew Anderson and Fink, {J. Lynn} and Oliver Holmes and Stephen Kazakoff and Conrad Leonard and Felicity Newell and Nick Waddell and Scott Wood and Mead, {Ronald S.} and Qinying Xu and Jianmin Wu and Mark Pinese and Cowley, {Mark J.} and Jones, {Marc D.} and Nagrial, {Adnan M.} and Chin, {Venessa T.} and Chantrill, {Lorraine A.} and Amanda Mawson and Angela Chou and Scarlett, {Christopher J.} and Pinho, {Andreia V.} and Ilse Rooman and Marc Giry-Laterriere and Samra, {Jaswinder S.} and Kench, {James G.} and Merrett, {Neil D.} and Toon, {Christopher W.} and Krishna Epari and Nguyen, {Nam Q.} and Andrew Barbour and Nikolajs Zeps and Jamieson, {Nigel B.} and McKay, {Colin J.} and Carter, {C. Ross} and Dickson, {Euan J.} and Graham, {Janet S.} and Fraser Duthie and Karin Oien and Jane Hair and Morton, {Jennifer P.} and Sansom, {Owen J.} and Robert Gr{\"u}tzmann and Hruban, {Ralph H.} and Anirban Maitra and Iacobuzio-Donahue, {Christine A.} and Schulick, {Richard D.} and Wolfgang, {Christopher L.} and Morgan, {Richard A.} and Lawlor, {Rita T.} and Borislav Rusev and Vincenzo Corbo and Roberto Salvia and Ivana Cataldo and Giampaolo Tortora and Tempero, {Margaret A.} and {Australian Pancreatic Cancer Genome Initiative} and Oliver Hofmann and Eshleman, {James R.} and Christian Pilarsky and Aldo Scarpa and Musgrove, {Elizabeth A.} and Gill, {Anthony J.} and Pearson, {John V.} and Grimmond, {Sean M.} and Nicola Waddell and Biankin, {Andrew V.}",

year = "2017",

doi = "10.1053/j.gastro.2016.09.060",

language = "English",

volume = "152",

pages = "68--74",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "Elsevier",

number = "1",

}

Humphris, JL, Patch, A-M, Nones, K, Bailey, PJ, Johns, AL, McKay, S, Chang, DK, Miller, DK, Pajic, M, Kassahn, KS, Quinn, MCJ, Bruxner, TJC, Christ, AN, Harliwong, I, Idrisoglu, S, Manning, S, Nourse, C, Nourbakhsh, E, Stone, A, Wilson, PJ, Anderson, M, Fink, JL, Holmes, O, Kazakoff, S, Leonard, C, Newell, F, Waddell, N, Wood, S, Mead, RS, Xu, Q, Wu, J, Pinese, M, Cowley, MJ, Jones, MD, Nagrial, AM, Chin, VT, Chantrill, LA, Mawson, A, Chou, A, Scarlett, CJ, Pinho, AV, Rooman, I, Giry-Laterriere, M, Samra, JS, Kench, JG, Merrett, ND, Toon, CW, Epari, K, Nguyen, NQ, Barbour, A, Zeps, N, Jamieson, NB, McKay, CJ, Carter, CR, Dickson, EJ, Graham, JS, Duthie, F, Oien, K, Hair, J, Morton, JP, Sansom, OJ, Grützmann, R, Hruban, RH, Maitra, A, Iacobuzio-Donahue, CA, Schulick, RD, Wolfgang, CL, Morgan, RA, Lawlor, RT, Rusev, B, Corbo, V, Salvia, R, Cataldo, I, Tortora, G, Tempero, MA, Australian Pancreatic Cancer Genome Initiative, Hofmann, O, Eshleman, JR, Pilarsky, C, Scarpa, A, Musgrove, EA, Gill, AJ, Pearson, JV, Grimmond, SM, Waddell, N & Biankin, AV 2017, 'Hypermutation in pancreatic cancer', Gastroenterology, vol. 152, no. 1, pp. 68-74. https://doi.org/10.1053/j.gastro.2016.09.060

TY - JOUR

T1 - Hypermutation in pancreatic cancer

AU - Humphris, Jeremy L.

AU - Patch, Ann-Marie

AU - Nones, Katia

AU - Bailey, Peter J.

AU - Johns, Amber L.

AU - McKay, Skye

AU - Chang, David K.

AU - Miller, David K.

AU - Pajic, Marina

AU - Kassahn, Karin S.

AU - Quinn, Michael C. J.

AU - Bruxner, Timothy J. C.

AU - Christ, Angelika N.

AU - Harliwong, Ivon

AU - Idrisoglu, Senel

AU - Manning, Suzanne

AU - Nourse, Craig

AU - Nourbakhsh, Ehsan

AU - Stone, Andrew

AU - Wilson, Peter J.

AU - Anderson, Matthew

AU - Fink, J. Lynn

AU - Holmes, Oliver

AU - Kazakoff, Stephen

AU - Leonard, Conrad

AU - Newell, Felicity

AU - Waddell, Nick

AU - Wood, Scott

AU - Mead, Ronald S.

AU - Xu, Qinying

AU - Wu, Jianmin

AU - Pinese, Mark

AU - Cowley, Mark J.

AU - Jones, Marc D.

AU - Nagrial, Adnan M.

AU - Chin, Venessa T.

AU - Chantrill, Lorraine A.

AU - Mawson, Amanda

AU - Chou, Angela

AU - Scarlett, Christopher J.

AU - Pinho, Andreia V.

AU - Rooman, Ilse

AU - Giry-Laterriere, Marc

AU - Samra, Jaswinder S.

AU - Kench, James G.

AU - Merrett, Neil D.

AU - Toon, Christopher W.

AU - Epari, Krishna

AU - Nguyen, Nam Q.

AU - Barbour, Andrew

AU - Zeps, Nikolajs

AU - Jamieson, Nigel B.

AU - McKay, Colin J.

AU - Carter, C. Ross

AU - Dickson, Euan J.

AU - Graham, Janet S.

AU - Duthie, Fraser

AU - Oien, Karin

AU - Hair, Jane

AU - Morton, Jennifer P.

AU - Sansom, Owen J.

AU - Grützmann, Robert

AU - Hruban, Ralph H.

AU - Maitra, Anirban

AU - Iacobuzio-Donahue, Christine A.

AU - Schulick, Richard D.

AU - Wolfgang, Christopher L.

AU - Morgan, Richard A.

AU - Lawlor, Rita T.

AU - Rusev, Borislav

AU - Corbo, Vincenzo

AU - Salvia, Roberto

AU - Cataldo, Ivana

AU - Tortora, Giampaolo

AU - Tempero, Margaret A.

AU - Australian Pancreatic Cancer Genome Initiative, null

AU - Hofmann, Oliver

AU - Eshleman, James R.

AU - Pilarsky, Christian

AU - Scarpa, Aldo

AU - Musgrove, Elizabeth A.

AU - Gill, Anthony J.

AU - Pearson, John V.

AU - Grimmond, Sean M.

AU - Waddell, Nicola

AU - Biankin, Andrew V.

PY - 2017

Y1 - 2017

N2 - Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

AB - Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

KW - cancer

KW - cancer genetics

KW - pancreas

UR - http://handle.westernsydney.edu.au:8081/1959.7/uws:38539

U2 - 10.1053/j.gastro.2016.09.060

DO - 10.1053/j.gastro.2016.09.060

M3 - Article

SN - 0016-5085

VL - 152

SP - 68

EP - 74

JO - Gastroenterology

JF - Gastroenterology

IS - 1

ER -

Hypermutation in pancreatic cancer

Abstract

Keywords

UN SDGs

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