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Circulating Cell-Free Tumor DNA Analysis of 50 Genes by Next-Generation Sequencing in the Prospective MOSCATO Trial
Clinical cancer research, 2016-06, Vol.22 (12), p.2960-2968
Jovelet, Cécile
Ileana, Ecaterina
Le Deley, Marie-Cécile
Motté, Nelly
Rosellini, Silvia
Romero, Alfredo
Lefebvre, Celine
Pedrero, Marion
Pata-Merci, Noémie
Droin, Nathalie
Deloger, Marc
Massard, Christophe
Hollebecque, Antoine
Ferté, Charles
Boichard, Amélie
Postel-Vinay, Sophie
Ngo-Camus, Maud
De Baere, Thierry
Vielh, Philippe
Scoazec, Jean-Yves
Vassal, Gilles
Eggermont, Alexander
André, Fabrice
Soria, Jean-Charles
Lacroix, Ludovic
2016
Details
Autor(en) / Beteiligte
Jovelet, Cécile
Ileana, Ecaterina
Le Deley, Marie-Cécile
Motté, Nelly
Rosellini, Silvia
Romero, Alfredo
Lefebvre, Celine
Pedrero, Marion
Pata-Merci, Noémie
Droin, Nathalie
Deloger, Marc
Massard, Christophe
Hollebecque, Antoine
Ferté, Charles
Boichard, Amélie
Postel-Vinay, Sophie
Ngo-Camus, Maud
De Baere, Thierry
Vielh, Philippe
Scoazec, Jean-Yves
Vassal, Gilles
Eggermont, Alexander
André, Fabrice
Soria, Jean-Charles
Lacroix, Ludovic
Titel
Circulating Cell-Free Tumor DNA Analysis of 50 Genes by Next-Generation Sequencing in the Prospective MOSCATO Trial
Ist Teil von
Clinical cancer research, 2016-06, Vol.22 (12), p.2960-2968
Ort / Verlag
United States
Erscheinungsjahr
2016
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
Liquid biopsies based on circulating cell-free DNA (cfDNA) analysis are described as surrogate samples for molecular analysis. We evaluated the concordance between tumor DNA (tDNA) and cfDNA analysis on a large cohort of patients with advanced or metastatic solid tumor, eligible for phase I trial and with good performance status, enrolled in MOSCATO 01 trial (clinical trial NCT01566019). Blood samples were collected at inclusion and cfDNA was extracted from plasma for 334 patients. Hotspot mutations were screened using next-generation sequencing for 50 cancer genes. Among the 283 patients with tDNA-cfDNA pairs, 121 had mutation in both, 99 in tumor only, 5 in cfDNA only, and for 58 patients no mutation was detected, leading to a 55.0% estimated sensitivity [95% confidence interval (CI), 48.4%-61.6%] at the patient level. Among the 220 patients with mutations in tDNA, the sensitivity of cfDNA analysis was significantly linked to the number of metastatic sites, albumin level, tumor type, and number of lines of treatment. A sensitivity prediction score could be derived from clinical parameters. Sensitivity is 83% in patients with a high score (≥8). In addition, we analyzed cfDNA for 51 patients without available tissue sample. Mutations were detected for 22 patients, including 19 oncogenic variants and 8 actionable mutations. Detection of somatic mutations in cfDNA is feasible for prescreening phase I candidates with a satisfactory specificity; overall sensitivity can be improved by a sensitivity score allowing to select patients for whom cfDNA constitutes a reliable noninvasive surrogate to screen mutations. Clin Cancer Res; 22(12); 2960-8. ©2016 AACR.
Sprache
Englisch
Identifikatoren
ISSN: 1078-0432
eISSN: 1557-3265
DOI: 10.1158/1078-0432.ccr-15-2470
Titel-ID: cdi_proquest_miscellaneous_1808698090
Format
–
Schlagworte
Adolescent
,
Adult
,
Aged
,
Biomarkers, Tumor - blood
,
Biomarkers, Tumor - genetics
,
Circulating Tumor DNA - genetics
,
Clinical Trials, Phase I as Topic
,
DNA Mutational Analysis - methods
,
DNA, Neoplasm - blood
,
DNA, Neoplasm - genetics
,
Female
,
High-Throughput Nucleotide Sequencing
,
Humans
,
Male
,
Middle Aged
,
Molecular Targeted Therapy
,
Mutation
,
Neoplasms - blood
,
Neoplasms - genetics
,
Patient Selection
,
Prospective Studies
,
Young Adult
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