Genomic analyses identify molecular subtypes of pancreatic cancer

Bailey, P. et al. (2016) Genomic analyses identify molecular subtypes of pancreatic cancer. Nature, 531(7592), pp. 47-52. (doi: 10.1038/nature16965) (PMID:26909576)

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Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Jamieson, Professor Nigel and Biankin, Professor Andrew and Miller, Mr David and Moran-Jones, Dr Kim and Nourse, Dr Craig and Graham, Dr Janet and Jones, Mr Marc and Hofmann, Dr Oliver and Bailey, Dr Peter and Bailey, Dr Ulla-Maja and Evers, Ms Lisa and Oien, Professor Karin and Musgrove, Dr Elizabeth and Grimmond, Professor Sean and Morton, Professor Jen and Chang, Professor David and Mincarelli, Dr Laura and Sansom, Professor Owen
Authors: Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., Nourse, C., Murtaugh, L. C., Harliwong, I., Idrisoglu, S., Manning, S., Nourbakhsh, E., Wani, S., Fink, L., Holmes, O., Chin, V., Anderson, M. J., Kazakoff, S., Leonard, C., Newell, F., Waddell, N., Wood, S., Xu, Q., Wilson, P. J., Cloonan, N., Kassahn, K. S., Taylor, D., Quek, K., Robertson, A., Pantano, L., Mincarelli, L., Sanchez, L. N., Evers, L., Wu, J., Pinese, M., Cowley, M. J., Jones, M. D., Colvin, E. K., Nagrial, A. M., Humphrey, E. S., Chantrill, L. A., Mawson, A., Humphris, J., Chou, A., Pajic, M., Scarlett, C. J., Pinho, A. V., Giry-Laterriere, M., Rooman, I., Samra, J. S., Kench, J. G., Lovell, J. A., Merrett, N. D., Toon, C. W., Epari, K., Nguyen, N. Q., Barbour, A., Zeps, N., Moran-Jones, K., Jamieson, N. B., Graham, J. S., Duthie, F., Oien, K., Hair, J., Grützmann, R., Maitra, A., Iacobuzio-Donahue, C. A., Wolfgang, C. L., Morgan, R. A., Lawlor, R. T., Corbo, V., Bassi, C., Rusev, B., Capelli, P., Salvia, R., Tortora, G., Mukhopadhyay, D., Petersen, G. M., Munzy, D. M., Fisher, W. E., Karim, S. A., Eshleman, J. R., Hruban, R. H., Pilarsky, C., Morton, J. P., Sansom, O. J., Scarpa, A., Musgrove, E. A., Bailey, U.-M. H., Hofmann, O., Sutherland, R. L., Wheeler, D. A., Gill, A. J., Gibbs, R. A., Pearson, J. V., Waddell, N., Biankin, A. V., and Grimmond, S. M.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Nature
Publisher:Nature Publishing Group
ISSN (Online):1476-4687
Published Online:24 February 2016
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
647981CR-UK Centre renewalKaren VousdenCancer Research UK (CAN-RES-UK)18076RI CANCER SCIENCES
656911Defining Platinum and PARP Responsive Molecular Phenotypes of Pancreatic Cancer.Andrew BiankinWellcome Trust (WELLCOME)103721/Z/14/ZICS - TRANSLATIONAL RESEARCH CENTRE
645511Genotype Guided Stratified Therapy for Pancreatic CancerAndrew BiankinCancer Research UK (CAN-RES-UK)17263ICS - TRANSLATIONAL RESEARCH CENTRE
698991Genotype Guided Stratified Therapy for Pancreatic CancerAndrew BiankinCancer Research UK (CAN-RES-UK)17263ICS - TRANSLATIONAL RESEARCH CENTRE
690421Glasgow Molecular Pathology (GMP) NodeKarin OienMedical Research Council (MRC)MR/N005813/1ICS - EXPERIMENTAL THERAPEUTICS