Genomic analyses identify molecular subtypes of pancreatic cancer

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJC, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Moran-Jones K, Jamieson NB, Graham JS, Duthie F, Oien K, Hair J, Grützmann R, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Rusev B, Capelli P, Salvia R, Tortora G, Mukhopadhyay D, Petersen GM, Munzy DM, Fisher WE, Karim SA, Eshleman JR, Hruban RH, Pilarsky C, Morton JR, Sansom OJ, Scarpa A, Musgrove EA, Bailey UMH, Hofmann O, Sutherland RL, Wheeler DA, Gill AJ, Gibbs RA, Pearson JV, Waddell N, Biankin AV, Grimmond SM, Pilarsky C
Zeitschrift: Nature
Jahr der Veröffentlichung: 2016
Band: 531
Heftnummer: 7592
Seitenbereich: 47-52
ISSN: 0028-0836


Abstract


Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-?, 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.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Grützmann, Robert Prof. Dr.
Lehrstuhl für Allgemein- und Viszeralchirurgie
Pilarsky, Christian Prof. Dr.
Professur für Chirurgische Forschung


Einrichtungen weiterer Autorinnen und Autoren

Beatson West of Scotland Cancer Centre (BWSCC)
Fiona Stanley Hospital
Harvard University
Houston Texas Medical Center
Johns Hopkins University
Kinghorn Cancer Centre
Mayo Clinic
Memorial Sloan Kettering Cancer Center
NHS Greater Glasgow and Clyde
Princess Alexandra Hospital
Royal Adelaide Hospital
Royal North Shore Hospital (RNSH)
Technische Universität Dresden
University Hospital of Verona
University of Glasgow
University of New South Wales (UNSW)
University of Queensland
University of Texas Medical Branch (UTMB)
University of Utah
University of Verona / Università degli Studi di Verona
University of Western Australia (UWA)


Zitierweisen

APA:
Bailey, P., Chang, D.K., Nones, K., Johns, A.L., Patch, A.-M., Gingras, M.-C.,... Pilarsky, C. (2016). Genomic analyses identify molecular subtypes of pancreatic cancer. Nature, 531(7592), 47-52. https://dx.doi.org/10.1038/nature16965

MLA:
Bailey, Peter, et al. "Genomic analyses identify molecular subtypes of pancreatic cancer." Nature 531.7592 (2016): 47-52.

BibTeX: 

Zuletzt aktualisiert 2018-10-10 um 02:18