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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F16%3AN0000057" target="_blank" >RIV/00209805:_____/16:N0000057 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/16:00093898 RIV/00216208:11110/16:10330365 RIV/61989592:15110/16:33160566 RIV/61988987:17110/16:A21026YM

Výsledek na webu

<a href="http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path" target="_blank" >http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.18632/oncotarget.12386" target="_blank" >10.18632/oncotarget.12386</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 cena should be further assessed in large case-control series.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 cena should be further assessed in large case-control series.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

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Projekt

<a href="/cs/project/NR9029" target="_blank" >NR9029: Epidemiologická studie genetických a behaviorálních rizikových faktorů karcinomu pankreatu</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Oncotarget

ISSN

1949-2553

e-ISSN

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Svazek periodika

7

Číslo periodika v rámci svazku

48

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

78827-78840

Kód UT WoS článku

000389636000052

EID výsledku v databázi Scopus

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