Hypermutation In Pancreatic Cancer

© 2017 AGA Institute 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 hypermut...

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Main Authors:	Humphris, J., Patch, A., Nones, K., Bailey, P., Johns, A., Mckay, S., Chang, D., Miller, D., Pajic, M., Kassahn, K., Quinn, M., Bruxner, T., Christ, A., Harliwong, I., Idrisoglu, S., Manning, S., Nourse, C., Nourbakhsh, E., Stone, A., Wilson, P., Anderson, M., Fink, J., Holmes, O., Kazakoff, S., Leonard, C., Newell, F., Waddell, N., Wood, S., Mead, R., Xu, Q., Wu, J., Pinese, M., Cowley, M., Jones, M., Nagrial, A., Chin, V., Chantrill, L., Mawson, A., Chou, A., Scarlett, C., Pinho, A., Rooman, I., Giry-Laterriere, M., Samra, J., Kench, J., Merrett, N., Toon, C., Epari, K., Nguyen, N., Barbour, A., Zeps, Nikolajs, Jamieson, N., McKay, C., Carter, C., Dickson, E., Graham, J., Duthie, F., Oien, K., Hair, J., Morton, J., Sansom, O., Gruetzmann, R., Hruban, R., Maitra, A., Iacobuzio-Donahue, C., Schulick, R., Wolfgang, C., Morgan, R., Lawlor, R., Rusev, B., Corbo, V., Salvia, R., Cataldo, I., Tortora, G., Tempero, M., Hofmann, O., Eshleman, J., Pilarsky, C., Scarpa, A., Musgrove, E., Gill, A., Pearson, J., Grimmond, S., Biankin, A.
Format:	Journal Article
Published:	W.B. Saunders Co. 2017
Online Access:	http://hdl.handle.net/20.500.11937/70852

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author	Humphris, J. Patch, A. Nones, K. Bailey, P. Johns, A. Mckay, S. Chang, D. Miller, D. Pajic, M. Kassahn, K. Quinn, M. Bruxner, T. Christ, A. Harliwong, I. Idrisoglu, S. Manning, S. Nourse, C. Nourbakhsh, E. Stone, A. Wilson, P. Anderson, M. Fink, J. Holmes, O. Kazakoff, S. Leonard, C. Newell, F. Waddell, N. Wood, S. Mead, R. Xu, Q. Wu, J. Pinese, M. Cowley, M. Jones, M. Nagrial, A. Chin, V. Chantrill, L. Mawson, A. Chou, A. Scarlett, C. Pinho, A. Rooman, I. Giry-Laterriere, M. Samra, J. Kench, J. Merrett, N. Toon, C. Epari, K. Nguyen, N. Barbour, A. Zeps, Nikolajs Jamieson, N. McKay, C. Carter, C. Dickson, E. Graham, J. Duthie, F. Oien, K. Hair, J. Morton, J. Sansom, O. Gruetzmann, R. Hruban, R. Maitra, A. Iacobuzio-Donahue, C. Schulick, R. Wolfgang, C. Morgan, R. Lawlor, R. Rusev, B. Corbo, V. Salvia, R. Cataldo, I. Tortora, G. Tempero, M. Hofmann, O. Eshleman, J. Pilarsky, C. Scarpa, A. Musgrove, E. Gill, A. Pearson, J. Grimmond, S. Waddell, N. Biankin, A.
author_facet	Humphris, J. Patch, A. Nones, K. Bailey, P. Johns, A. Mckay, S. Chang, D. Miller, D. Pajic, M. Kassahn, K. Quinn, M. Bruxner, T. Christ, A. Harliwong, I. Idrisoglu, S. Manning, S. Nourse, C. Nourbakhsh, E. Stone, A. Wilson, P. Anderson, M. Fink, J. Holmes, O. Kazakoff, S. Leonard, C. Newell, F. Waddell, N. Wood, S. Mead, R. Xu, Q. Wu, J. Pinese, M. Cowley, M. Jones, M. Nagrial, A. Chin, V. Chantrill, L. Mawson, A. Chou, A. Scarlett, C. Pinho, A. Rooman, I. Giry-Laterriere, M. Samra, J. Kench, J. Merrett, N. Toon, C. Epari, K. Nguyen, N. Barbour, A. Zeps, Nikolajs Jamieson, N. McKay, C. Carter, C. Dickson, E. Graham, J. Duthie, F. Oien, K. Hair, J. Morton, J. Sansom, O. Gruetzmann, R. Hruban, R. Maitra, A. Iacobuzio-Donahue, C. Schulick, R. Wolfgang, C. Morgan, R. Lawlor, R. Rusev, B. Corbo, V. Salvia, R. Cataldo, I. Tortora, G. Tempero, M. Hofmann, O. Eshleman, J. Pilarsky, C. Scarpa, A. Musgrove, E. Gill, A. Pearson, J. Grimmond, S. Waddell, N. Biankin, A.
author_sort	Humphris, J.
building	Curtin Institutional Repository
collection	Online Access
description	© 2017 AGA Institute 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.
first_indexed	2025-11-14T10:45:43Z
format	Journal Article
id	curtin-20.500.11937-70852
institution	Curtin University Malaysia
institution_category	Local University
last_indexed	2025-11-14T10:45:43Z
publishDate	2017
publisher	W.B. Saunders Co.
recordtype	eprints
repository_type	Digital Repository
spelling	curtin-20.500.11937-708522018-12-13T09:33:09Z Hypermutation In Pancreatic Cancer Humphris, J. Patch, A. Nones, K. Bailey, P. Johns, A. Mckay, S. Chang, D. Miller, D. Pajic, M. Kassahn, K. Quinn, M. Bruxner, T. Christ, A. Harliwong, I. Idrisoglu, S. Manning, S. Nourse, C. Nourbakhsh, E. Stone, A. Wilson, P. Anderson, M. Fink, J. Holmes, O. Kazakoff, S. Leonard, C. Newell, F. Waddell, N. Wood, S. Mead, R. Xu, Q. Wu, J. Pinese, M. Cowley, M. Jones, M. Nagrial, A. Chin, V. Chantrill, L. Mawson, A. Chou, A. Scarlett, C. Pinho, A. Rooman, I. Giry-Laterriere, M. Samra, J. Kench, J. Merrett, N. Toon, C. Epari, K. Nguyen, N. Barbour, A. Zeps, Nikolajs Jamieson, N. McKay, C. Carter, C. Dickson, E. Graham, J. Duthie, F. Oien, K. Hair, J. Morton, J. Sansom, O. Gruetzmann, R. Hruban, R. Maitra, A. Iacobuzio-Donahue, C. Schulick, R. Wolfgang, C. Morgan, R. Lawlor, R. Rusev, B. Corbo, V. Salvia, R. Cataldo, I. Tortora, G. Tempero, M. Hofmann, O. Eshleman, J. Pilarsky, C. Scarpa, A. Musgrove, E. Gill, A. Pearson, J. Grimmond, S. Waddell, N. Biankin, A. © 2017 AGA Institute 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/70852 10.1053/j.gastro.2016.09.060 W.B. Saunders Co. restricted
spellingShingle	Humphris, J. Patch, A. Nones, K. Bailey, P. Johns, A. Mckay, S. Chang, D. Miller, D. Pajic, M. Kassahn, K. Quinn, M. Bruxner, T. Christ, A. Harliwong, I. Idrisoglu, S. Manning, S. Nourse, C. Nourbakhsh, E. Stone, A. Wilson, P. Anderson, M. Fink, J. Holmes, O. Kazakoff, S. Leonard, C. Newell, F. Waddell, N. Wood, S. Mead, R. Xu, Q. Wu, J. Pinese, M. Cowley, M. Jones, M. Nagrial, A. Chin, V. Chantrill, L. Mawson, A. Chou, A. Scarlett, C. Pinho, A. Rooman, I. Giry-Laterriere, M. Samra, J. Kench, J. Merrett, N. Toon, C. Epari, K. Nguyen, N. Barbour, A. Zeps, Nikolajs Jamieson, N. McKay, C. Carter, C. Dickson, E. Graham, J. Duthie, F. Oien, K. Hair, J. Morton, J. Sansom, O. Gruetzmann, R. Hruban, R. Maitra, A. Iacobuzio-Donahue, C. Schulick, R. Wolfgang, C. Morgan, R. Lawlor, R. Rusev, B. Corbo, V. Salvia, R. Cataldo, I. Tortora, G. Tempero, M. Hofmann, O. Eshleman, J. Pilarsky, C. Scarpa, A. Musgrove, E. Gill, A. Pearson, J. Grimmond, S. Waddell, N. Biankin, A. Hypermutation In Pancreatic Cancer
title	Hypermutation In Pancreatic Cancer
title_full	Hypermutation In Pancreatic Cancer
title_fullStr	Hypermutation In Pancreatic Cancer
title_full_unstemmed	Hypermutation In Pancreatic Cancer
title_short	Hypermutation In Pancreatic Cancer
title_sort	hypermutation in pancreatic cancer
url	http://hdl.handle.net/20.500.11937/70852

Hypermutation In Pancreatic Cancer

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