Defining the molecular pathology of pancreatic body and tail adenocarcinom

Dreyer, S.B., Jamieson, N.B. , Upstill-Goddard, R., Bailey, P.J. , McKay, C.J., Australian Pancreatic Cancer Genome Initiative, , Biankin, A.V. and Chang, D.K. (2018) Defining the molecular pathology of pancreatic body and tail adenocarcinom. British Journal of Surgery, 105(2), e183-e191. (doi:10.1002/bjs.10772) (PMID:29341146) (PMCID:PMC5817249)

Dreyer, S.B., Jamieson, N.B. , Upstill-Goddard, R., Bailey, P.J. , McKay, C.J., Australian Pancreatic Cancer Genome Initiative, , Biankin, A.V. and Chang, D.K. (2018) Defining the molecular pathology of pancreatic body and tail adenocarcinom. British Journal of Surgery, 105(2), e183-e191. (doi:10.1002/bjs.10772) (PMID:29341146) (PMCID:PMC5817249)

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Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) remains a dismal disease, with very little improvement in survival over the past 50 years. Recent large-scale genomic studies have improved understanding of the genomic and transcriptomic landscape of the disease, yet very little is known about molecular heterogeneity according to tumour location in the pancreas; body and tail PDACs especially tend to have a significantly worse prognosis. The aim was to investigate the molecular differences between PDAC of the head and those of the body and tail of the pancreas. Methods: Detailed correlative analysis of clinicopathological variables, including tumour location, genomic and transcriptomic data, was performed using the Australian Pancreatic Cancer Genome Initiative (APGI) cohort, part of the International Cancer Genome Consortium study. Results: Clinicopathological data were available for 518 patients recruited to the APGI, of whom 421 underwent genomic analyses; 179 of these patients underwent whole-genome and 96 RNA sequencing. Patients with tumours of the body and tail had significantly worse survival than those with pancreatic head tumours (12·1 versus 22·0 months; P = 0·001). Location in the body and tail was associated with the squamous subtype of PDAC. Body and tail PDACs enriched for gene programmes involved in tumour invasion and epithelial-to-mesenchymal transition, as well as features of poor antitumour immune response. Whether this is due to a molecular predisposition from the outset, or reflects a later time point on the tumour molecular clock, requires further investigation using well designed prospective studies in pancreatic cancer. Conclusion: PDACs of the body and tail demonstrate aggressive tumour biology that may explain worse clinical outcomes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jamieson, Dr Nigel and Dreyer, Dr Stephan and Biankin, Professor Andrew and Bailey, Dr Peter and Upstill-Goddard, Dr Rosanna and McKay, Mr Colin and Chang, Dr David
Authors: Dreyer, S.B., Jamieson, N.B., Upstill-Goddard, R., Bailey, P.J., McKay, C.J., Australian Pancreatic Cancer Genome Initiative, , Biankin, A.V., and Chang, D.K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:British Journal of Surgery
Publisher:Wiley
ISSN:0007-1323
ISSN (Online):1365-2168
Published Online:17 January 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in British Journal of Surgery 105(2): e183-e191
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656911Defining Platinum and PARP Responsive Molecular Phenotypes of Pancreatic Cancer.Andrew BiankinWellcome Trust (WELLCOTR)103721/Z/14/ZICS - TRANSLATIONAL RESEARCH CENTRE
645513Genotype Guided Stratified Therapy for Pancreatic CancerAndrew BiankinCancer Research UK (CRUK)17263ICS - TRANSLATIONAL RESEARCH CENTRE
647984CR-UK Centre renewalKaren VousdenCancer Research UK (CRUK)18076RI CANCER SCIENCES
712701Clinical Training Award Cycle 2Andrew BiankinCancer Research UK (CRUK)20921ICS - TRANSLATIONAL RESEARCH CENTRE
690421Glasgow Molecular Pathology (GMP) NodeKarin OienMedical Research Council (MRC)MR/N005813/1ICS - EXPERIMENTAL THERAPEUTICS