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Verfasst von:Jilg, Stefanie [VerfasserIn]   i
 Gaiser, Timo [VerfasserIn]   i
 Hohenberger, Peter [VerfasserIn]   i
Titel:Circulating cKIT and PDGFRA DNA indicates disease activity in gastrointestinal stromal tumor (GIST)
Verf.angabe:Stefanie Jilg, Michael Rassner, Jacqueline Maier, Silvia Waldeck, Victoria Kehl, Marie Follo, Ulrike Philipp, Andreas Sauter, Katja Specht, Jan Mitschke, Thoralf Lange, Sebastian Bauer, Philipp J. Jost, Christian Peschel, Justus Duyster, Timo Gaiser, Peter Hohenberger and Nikolas von Bubnoff
E-Jahr:2019
Jahr:Online 18 Mar 2019
Umfang:13 S.
Fussnoten:Gesehen am 21.10.2019
Titel Quelle:Enthalten in: International journal of cancer
Ort Quelle:Bognor Regis : Wiley-Liss, 1966
Jahr Quelle:2019
Band/Heft Quelle:145(2019), 8, Seite 2292-2303
ISSN Quelle:1097-0215
Abstract:This prospective trial aimed to investigate whether tumor-specific cKIT and PDGFRA mutations can be detected and quantified in circulating tumor (ct)DNA in patients with active GIST, and whether detection indicates disease activity. We included 25 patients with active disease and cKIT or PDGFRA mutations detected in tissue. Mutant ctDNA was detected in the peripheral blood plasma using allele-specific ligation (L-)PCR and droplet digital (d)PCR. CtDNA harboring tumor-specific cKIT or PDGFRA mutations was detected at least once in 16 out of 25 patients using L-PCR (64%) and in 20 out of 25 patients with dPCR (80%). Using dPCR, the absolute numbers of ctDNA fragments (DNA copies/ml) and the mutant allele frequency (MAF; in percent of wild-type control) strongly correlated with tumor size expressed as RECIST1.1 sum of diameter (SOD) in mm (ρ = 0.3719 and 0.408, respectively, p < 0.0001) and response status (ρ = 0.3939 and 0.392, respectively, p < 0.0001 and p < 0.001). Specificity of dPCR for detection of progression was 79.2% with a sensitivity of 55.2% and dPCR discriminated CR from active disease with a specificity of 96% and s sensitivity of 44.7%. With L-PCR, correlations of MAF with tumor size and response status were less prominent. Serial ctDNA measurement reflected individual disease courses over time. Targeted panel sequencing of four patients detected additional driver mutations in all cases and secondary resistance mutations in two cases. Thus, ctDNA indicates disease activity in patients with GIST and should be incorporated as companion biomarker in future prospective trials.
DOI:doi:10.1002/ijc.32282
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1002/ijc.32282
 Verlag: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.32282
 DOI: https://doi.org/10.1002/ijc.32282
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:cancer biomarker
 circulating tumor DNA
 GIST
 liquid biopsy
K10plus-PPN:1679249428
Verknüpfungen:→ Zeitschrift

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