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dc.contributor.authorMohan, Sumitra
dc.contributor.authorAyub, Mahmood
dc.contributor.authorRothwell, Dominic G
dc.contributor.authorGulati, Sakshi
dc.contributor.authorKilerci, Bedirhan
dc.contributor.authorHollebecque, Antoine,
dc.contributor.authorLeong, Hui Sun
dc.contributor.authorSmith, Nigel K
dc.contributor.authorSahoo, Sudhakar
dc.contributor.authorDescamps, Tine
dc.contributor.authorZhou, Cong
dc.contributor.authorHubner, Richard A
dc.contributor.authorMcNamara, Mairead G
dc.contributor.authorLamarca, Angela
dc.contributor.authorValle, Juan W
dc.contributor.authorDive, Caroline
dc.contributor.authorBrady, Ged
dc.date.accessioned2019-10-04T09:48:28Z
dc.date.available2019-10-04T09:48:28Z
dc.date.issued2019en
dc.identifier.citationMohan S, Ayub M, Rothwell DG, Gulati S, Kilerci B, Hollebecque A, et al. Analysis of circulating cell-free DNA identifies KRAS copy number gain and mutation as a novel prognostic marker in pancreatic cancer. Sci Rep. 2019 Aug 12;9(1):11610.en
dc.identifier.pmid31406261en
dc.identifier.doi10.1038/s41598-019-47489-7en
dc.identifier.urihttp://hdl.handle.net/10541/622137
dc.description.abstractSerial biopsy of pancreatic ductal adenocarcinoma (PDAC), to chart tumour evolution presents a significant challenge. We examined the utility of circulating free DNA (cfDNA) as a minimally invasive approach across a cohort of 55 treatment-naïve patients with PDAC; 31 with metastatic and 24 with locally advanced disease. Somatic mutations in cfDNA were detected using next generation sequencing in 15/24 (62.5%) and 27/31 (87%) of patients with locally advanced and metastatic disease, respectively. Copy number changes were detected in cfDNA of 10 patients of whom 7 exhibited gain of chromosome 12p harbouring KRAS as well as a canonical KRAS codon 12 mutation. In multivariable Cox Regression analysis, we show for the first time that patients with KRAS copy number gain and KRAS mutation have significantly worse outcomes, suggesting that this may be linked to PDAC progression. The simple cfDNA assay we describe will enable determination of the presence of KRAS copy number gain and KRAS mutations in larger studies and clinical trials.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1038/s41598-019-47489-7en
dc.titleAnalysis of circulating cell-free DNA identifies KRAS copy number gain and mutation as a novel prognostic marker in pancreatic canceren
dc.typeArticleen
dc.contributor.departmentClinical Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, Alderley Park, SK10 4TGen
dc.identifier.journalScientific Reportsen
dc.description.noteen]
refterms.dateFOA2019-10-07T21:07:32Z


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