Journal
BRITISH JOURNAL OF SURGERY
Volume 105, Issue 2, Pages E183-E191Publisher
OXFORD UNIV PRESS
DOI: 10.1002/bjs.10772
Keywords
-
Categories
Funding
- Wellcome Trust Senior Investigator Award [103721/Z/14/Z]
- Cancer Research UK Programme Grant [C29717/A17263, C29717/A18484]
- Cancer Research UK Glasgow Centre [C596/A18076]
- Cancer Research UK Clinical Training Award [C596/A20921]
- Scottish Genome Partnership [SEHHD-CSO 1175759/2158447]
- Medical Research Council/Engineering and Physical Sciences Research Programme Glasgow Molecular Pathology Node
- Howat Foundation
- Precision Panc
- National Health and Medical Research Council of Australia
- Cancer Council New South Wales, Cancer Institute New South Wales
- Royal Australasian College of Surgeons
- St Vincent's Clinic Foundation
- R. T. Hall Trust
- Avner Pancreatic Cancer Foundation
- MRC [MR/N005813/1] Funding Source: UKRI
- Academy of Medical Sciences (AMS) [AMS-SGCL9-Jamieson] Funding Source: researchfish
- Cancer Research UK [17263, 23526, 22533] Funding Source: researchfish
- Medical Research Council [MR/N005813/1] Funding Source: researchfish
- Wellcome Trust [103721/Z/14/Z] Funding Source: researchfish
- Pancreatic Cancer UK [FLF2015_04_Glasgow, RIF2015_A06_Jamieson] Funding Source: researchfish
Ask authors/readers for more resources
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, or 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available