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

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CALVEZ-KELM Florence Le FOLL Matthieu WOZNIAK Magdalena B. DELHOMME Tiffany M. DURAND Geoffroy CHOPARD Priscilia PERTESI Maroulio FABIANOVA Eleonora ADAMCAKOVA Zora HOLCATOVA Ivana FORETOVÁ Lenka JANOUT Vladimir VALLEE Maxime P. RINALDI Sabina BRENNAN Paul MCKAY James D. BYRNES Graham B. SCELO Ghislaine

Rok publikování 2016
Druh Článek v odborném periodiku
Časopis / Zdroj Oncotarget
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Doi http://dx.doi.org/10.18632/oncotarget.12386
Obor Onkologie a hematologie
Klíčová slova cell-free DNA; KRAS mutations; plasma; pancreatic cancer detection
Popis 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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