Detection of mutant-free circulating tumor DNA in the plasma of patients with gastrointestinal stromal tumor (GIST) harboring activating mutations of C-Kit or PDGFRA.

Session Type and Session Title: 
Poster Discussion Session, Sarcoma
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 10508)
Nikolas von Bubnoff, Irina Kerle, Katja Specht, Melanie Bruegel, Claudia Wickenhauser, Philipp Jost, Dietger Niederwieser, Christian Peschel, Justus Duyster, Thoralf Lange, Jacqueline Maier; Universitaetsklinikum Freiburg, Freiburg, Germany; Technische Universitaet Muenchen, Muenchen, Germany; Insitute of Pathology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Universitaetsklinikum Leipzig, Leipzig, Germany; University of Leipzig, Leipzig, Germany

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Abstract Disclosures


Background: In gastrointestinal stromal tumor (GIST), there is no biomarker available that indicates success or failure of therapy. We hypothesized that tumor specific CKIT or PDGFRA mutant DNA fragments can be detected and quantified in plasma samples of GIST patients. Methods: We prospectively collected 291 plasma samples from 38 subjects with GIST harbouring activating mutations of CKIT or PDGFRA detected in tumor tissue, irrespective of current disease status or treatment. We used allele-specific Ligation PCR to detect mutant free circulating (fc)DNA. Results: We were able to detect fcDNA harbouring the tumor mutation in 15 out of 38 patients. Patients with active disease displayed significantly higher amounts of mutant fcDNA compared to patients in CR. The amount of mutant fcDNA correlated with disease course. We observed repeated positive test results or an increase of mutant fcDNA in five patients with progressive disease or relapse. A decline of tumor fcDNA or conversion from positive to negative was seen in five patients responding to treatment. A negative to positive conversion was seen in two patients with relapse and one patient with progression. In two cases, we aimed to identify additional mutations, and found four additional exchanges, including mutations not known from sequentially performed tumor biopsies. Conclusions: Our results indicate that free circulating DNA harbouring tumor specific mutations in the plasma of patients with GIST can be used as tumor-specific biomarker. The detection of resistance mutations in plasma samples might allow earlier treatment changes and obviates the need for repeated tumor biopsies. Clinical trial information: NCT01462994.