Oncotarget

Research Papers:

KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control

Florence Le Calvez-Kelm _, Matthieu Foll, Magdalena B. Wozniak, Tiffany M. Delhomme, Geoffroy Durand, Priscilia Chopard, Maroulio Pertesi, Eleonora Fabianova, Zora Adamcakova, Ivana Holcatova, Lenka Foretova, Vladimir Janout, Maxime P. Vallee, Sabina Rinaldi, Paul Brennan, James D. McKay, Graham B. Byrnes and Ghislaine Scelo

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Oncotarget. 2016; 7:78827-78840. https://doi.org/10.18632/oncotarget.12386

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Abstract

Florence Le Calvez-Kelm1, Matthieu Foll1, Magdalena B. Wozniak1, Tiffany M. Delhomme1, Geoffroy Durand1, Priscilia Chopard1, Maroulio Pertesi1, Eleonora Fabianova2, Zora Adamcakova2, Ivana Holcatova3, Lenka Foretova4, Vladimir Janout5,6, Maxime P. Vallee1, Sabina Rinaldi1, Paul Brennan1, James D. McKay1, Graham B. Byrnes1, Ghislaine Scelo1

1International Agency for Research on Cancer (IARC), Lyon, France

2Regional Authority of Public Health, Banska Bystrica, Slovakia

3Charles University of Prague, First Faculty of Medicine, Institute of Hygiene and Epidemiology, Prague, Czech Republic

4Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Brno, Czech Republic

5Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic

6Faculty of Medicine, University of Ostrava, Czech Republic

Correspondence to:

Florence Le Calvez-Kelm, email: lecalvez@iarc.fr

Keywords: cell-free DNA, KRAS mutations, plasma, pancreatic cancer detection

Received: June 29, 2016    Accepted: September 19, 2016    Published: October 1, 2016

ABSTRACT

The utility of KRAS mutations in plasma circulating cell-free DNA (cfDNA) samples as non-invasive biomarkers for the detection of pancreatic cancer has never been evaluated in a large case-control series. We applied a KRAS amplicon-based deep sequencing strategy combined with analytical pipeline specifically designed for the detection of low-abundance mutations to screen plasma samples of 437 pancreatic cancer cases, 141 chronic pancreatitis subjects, and 394 healthy controls. We detected mutations in 21.1% (N=92) of cases, of whom 82 (89.1%) carried at least one mutation at hotspot codons 12, 13 or 61, with mutant allelic fractions from 0.08% to 79%. Advanced stages were associated with an increased proportion of detection, with KRAS cfDNA mutations detected in 10.3%, 17,5% and 33.3% of cases with local, regional and systemic stages, respectively. We also detected KRAS cfDNA mutations in 3.7% (N=14) of healthy controls and in 4.3% (N=6) of subjects with chronic pancreatitis, but at significantly lower allelic fractions than in cases. Combining cfDNA KRAS mutations and CA19-9 plasma levels on a limited set of case-control samples did not improve the overall performance of the biomarkers as compared to CA19-9 alone. Whether the limited sensitivity and specificity observed in our series of KRAS mutations in plasma cfDNA as biomarkers for pancreatic cancer detection are attributable to methodological limitations or to the biology of cfDNA should be further assessed in large case-control series.


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