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KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control
F. Le Calvez-Kelm, M. Foll, MB. Wozniak, TM. Delhomme, G. Durand, P. Chopard, M. Pertesi, E. Fabianova, Z. Adamcakova, I. Holcatova, L. Foretova, V. Janout, MP. Vallee, S. Rinaldi, P. Brennan, JD. McKay, GB. Byrnes, G. Scelo,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, multicentrická studie, validační studie
NLK
Free Medical Journals
od 2010
PubMed Central
od 2010
Europe PubMed Central
od 2010
Open Access Digital Library
od 2010-01-01
- MeSH
- antigen CA-19-9 krev MeSH
- cirkulující nádorová DNA krev genetika MeSH
- duktální karcinom pankreatu krev genetika patologie MeSH
- fenotyp MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace * MeSH
- mutační analýza DNA MeSH
- nádorové biomarkery krev genetika MeSH
- nádory slinivky břišní krev genetika patologie MeSH
- pilotní projekty MeSH
- prediktivní hodnota testů MeSH
- protoonkogenní proteiny p21(ras) krev genetika MeSH
- reprodukovatelnost výsledků MeSH
- senioři MeSH
- staging nádorů MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- validační studie MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
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.
International Agency for Research on Cancer Lyon France
Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University Brno Czech Republic
Regional Authority of Public Health Banska Bystrica Slovakia
Citace poskytuje Crossref.org
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- $a 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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