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

J 2016

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

CALVEZ-KELM, Florence Le, Matthieu FOLL, Magdalena B. WOZNIAK, Tiffany M. DELHOMME, Geoffroy DURAND et. al.

Základní údaje

Originální název

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

Autoři

CALVEZ-KELM, Florence Le (250 Francie), Matthieu FOLL (250 Francie), Magdalena B. WOZNIAK (250 Francie), Tiffany M. DELHOMME (250 Francie), Geoffroy DURAND (250 Francie), Priscilia CHOPARD (250 Francie), Maroulio PERTESI (250 Francie), Eleonora FABIANOVA (703 Slovensko), Zora ADAMCAKOVA (703 Slovensko), Ivana HOLCATOVA (203 Česká republika), Lenka FORETOVÁ (203 Česká republika, garant, domácí), Vladimir JANOUT (203 Česká republika), Maxime P. VALLEE (250 Francie), Sabina RINALDI (250 Francie), Paul BRENNAN (250 Francie), James D. MCKAY (250 Francie), Graham B. BYRNES (250 Francie) a Ghislaine SCELO (250 Francie)

Vydání

Oncotarget, Albany, Impact Journals, 2016, 1949-2553

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 5.168

Kód RIV

RIV/00216224:14110/16:00093898

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.18632/oncotarget.12386

UT WoS

000389636000052

Klíčová slova anglicky

cell-free DNA; KRAS mutations; plasma; pancreatic cancer detection

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 10. 4. 2017 15:05, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

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.

Citovat

CALVEZ-KELM, Florence Le, Matthieu FOLL, Magdalena B. WOZNIAK, Tiffany M. DELHOMME, Geoffroy DURAND, Priscilia CHOPARD, Maroulio PERTESI, Eleonora FABIANOVA, Zora ADAMCAKOVA, Ivana HOLCATOVA, Lenka FORETOVÁ, Vladimir JANOUT, Maxime P. VALLEE, Sabina RINALDI, Paul BRENNAN, James D. MCKAY, Graham B. BYRNES a Ghislaine SCELO. KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control study. Oncotarget. Albany: Impact Journals, 2016, roč. 7, č. 48, s. 78827-78840. ISSN 1949-2553. Dostupné z: https://dx.doi.org/10.18632/oncotarget.12386.

@article{1375566,
   author = {CalvezandKelm, Florence Le and Foll, Matthieu and Wozniak, Magdalena B. and Delhomme, Tiffany M. and Durand, Geoffroy and Chopard, Priscilia and Pertesi, Maroulio and Fabianova, Eleonora and Adamcakova, Zora and Holcatova, Ivana and Foretová, Lenka and Janout, Vladimir and Vallee, Maxime P. and Rinaldi, Sabina and Brennan, Paul and McKay, James D. and Byrnes, Graham B. and Scelo, Ghislaine},
   article_location = {Albany},
   article_number = {48},
   doi = {http://dx.doi.org/10.18632/oncotarget.12386},
   keywords = {cell-free DNA; KRAS mutations; plasma; pancreatic cancer detection},
   language = {eng},
   issn = {1949-2553},
   journal = {Oncotarget},
   title = {KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control study},
   volume = {7},
   year = {2016}
}

TY  - JOUR
ID  - 1375566
AU  - 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
PY  - 2016
TI  - KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control study
JF  - Oncotarget
VL  - 7
IS  - 48
SP  - 78827-78840
EP  - 78827-78840
PB  - Impact Journals
SN  - 19492553
KW  - cell-free DNA
KW  - KRAS mutations
KW  - plasma
KW  - pancreatic cancer detection
N2  - 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.
ER  -

CALVEZ-KELM, Florence Le, Matthieu FOLL, Magdalena B. WOZNIAK, Tiffany M. DELHOMME, Geoffroy DURAND, Priscilia CHOPARD, Maroulio PERTESI, Eleonora FABIANOVA, Zora ADAMCAKOVA, Ivana HOLCATOVA, Lenka FORETOVÁ, Vladimir JANOUT, Maxime P. VALLEE, Sabina RINALDI, Paul BRENNAN, James D. MCKAY, Graham B. BYRNES a Ghislaine SCELO. KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control study. \textit{Oncotarget}. Albany: Impact Journals, 2016, roč.~7, č.~48, s.~78827-78840. ISSN~1949-2553. Dostupné z: https://dx.doi.org/10.18632/oncotarget.12386.

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