• Something wrong with this record ?

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,

. 2016 ; 7 (48) : 78827-78840.

Language English Country United States

Document type Journal Article, Multicenter Study, Validation Study

Persistent link   https://www.medvik.cz/link/bmc18011005

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc18011005
003      
CZ-PrNML
005      
20180404142452.0
007      
ta
008      
180404s2016 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.18632/oncotarget.12386 $2 doi
035    __
$a (PubMed)27705932
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Le Calvez-Kelm, Florence $u International Agency for Research on Cancer (IARC), Lyon, France.
245    10
$a KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control / $c 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,
520    9_
$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.
650    _2
$a senioři $7 D000368
650    _2
$a nádorové biomarkery $x krev $x genetika $7 D014408
650    _2
$a antigen CA-19-9 $x krev $7 D018395
650    _2
$a duktální karcinom slinivky břišní $x krev $x genetika $x patologie $7 D021441
650    _2
$a studie případů a kontrol $7 D016022
650    _2
$a cirkulující nádorová DNA $x krev $x genetika $7 D000074141
650    _2
$a Česká republika $7 D018153
650    _2
$a mutační analýza DNA $7 D004252
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a frekvence genu $7 D005787
650    _2
$a genetická predispozice k nemoci $7 D020022
650    _2
$a lidé $7 D006801
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    12
$a mutace $7 D009154
650    _2
$a staging nádorů $7 D009367
650    _2
$a nádory slinivky břišní $x krev $x genetika $x patologie $7 D010190
650    _2
$a fenotyp $7 D010641
650    _2
$a pilotní projekty $7 D010865
650    _2
$a prediktivní hodnota testů $7 D011237
650    _2
$a protoonkogenní proteiny p21(ras) $x krev $x genetika $7 D016283
650    _2
$a reprodukovatelnost výsledků $7 D015203
650    _2
$a Slovenská republika $7 D018154
655    _2
$a časopisecké články $7 D016428
655    _2
$a multicentrická studie $7 D016448
655    _2
$a validační studie $7 D023361
700    1_
$a Foll, Matthieu $u International Agency for Research on Cancer (IARC), Lyon, France.
700    1_
$a Wozniak, Magdalena B $u International Agency for Research on Cancer (IARC), Lyon, France.
700    1_
$a Delhomme, Tiffany M $u International Agency for Research on Cancer (IARC), Lyon, France.
700    1_
$a Durand, Geoffroy $u International Agency for Research on Cancer (IARC), Lyon, France.
700    1_
$a Chopard, Priscilia $u International Agency for Research on Cancer (IARC), Lyon, France.
700    1_
$a Pertesi, Maroulio $u International Agency for Research on Cancer (IARC), Lyon, France.
700    1_
$a Fabianova, Eleonora $u Regional Authority of Public Health, Banska Bystrica, Slovakia.
700    1_
$a Adamcakova, Zora $u Regional Authority of Public Health, Banska Bystrica, Slovakia.
700    1_
$a Holcatova, Ivana $u Charles University of Prague, First Faculty of Medicine, Institute of Hygiene and Epidemiology, Prague, Czech Republic.
700    1_
$a Foretova, Lenka $u Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Brno, Czech Republic.
700    1_
$a Janout, Vladimir $u Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic. Faculty of Medicine, University of Ostrava, Czech Republic.
700    1_
$a Vallee, Maxime P $u International Agency for Research on Cancer (IARC), Lyon, France.
700    1_
$a Rinaldi, Sabina $u International Agency for Research on Cancer (IARC), Lyon, France.
700    1_
$a Brennan, Paul $u International Agency for Research on Cancer (IARC), Lyon, France.
700    1_
$a McKay, James D $u International Agency for Research on Cancer (IARC), Lyon, France.
700    1_
$a Byrnes, Graham B $u International Agency for Research on Cancer (IARC), Lyon, France.
700    1_
$a Scelo, Ghislaine $u International Agency for Research on Cancer (IARC), Lyon, France.
773    0_
$w MED00184852 $t Oncotarget $x 1949-2553 $g Roč. 7, č. 48 (2016), s. 78827-78840
856    41
$u https://pubmed.ncbi.nlm.nih.gov/27705932 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20180404 $b ABA008
991    __
$a 20180404142531 $b ABA008
999    __
$a ok $b bmc $g 1288490 $s 1007817
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2016 $b 7 $c 48 $d 78827-78840 $i 1949-2553 $m Oncotarget $n Oncotarget $x MED00184852
LZP    __
$a Pubmed-20180404

Find record

Citation metrics

Archiving options