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Boonstra PA, Ter Elst A, Tibbesma M, et al. A single digital droplet PCR assay to detect multiple . Oncotarget. 2018;9(17):13870-13883doi: 10.18632/oncotarget.24493.
Boonstra, P. A., Ter Elst, A., Tibbesma, M., Bosman, L. J., Mathijssen, R., Atrafi, F., van Coevorden, F., Steeghs, N., Farag, S., Gelderblom, H., van der Graaf, W. T. A., Desar, I. M. E., Maier, J., Overbosch, J., Suurmeijer, A. J. H., Gietema, J., Schuuring, E., & Reyners, A. K. L. (2018). A single digital droplet PCR assay to detect multiple . Oncotarget, 9(17), 13870-13883. https://doi.org/10.18632/oncotarget.24493
Boonstra, Pieter A, et al. "A single digital droplet PCR assay to detect multiple ." Oncotarget vol. 9,17 (2018): 13870-13883. doi: https://doi.org/10.18632/oncotarget.24493
Boonstra PA, Ter Elst A, Tibbesma M, Bosman LJ, Mathijssen R, Atrafi F, van Coevorden F, Steeghs N, Farag S, Gelderblom H, van der Graaf WTA, Desar IME, Maier J, Overbosch J, Suurmeijer AJH, Gietema J, Schuuring E, Reyners AKL. A single digital droplet PCR assay to detect multiple . Oncotarget. 2018 Feb 14;9(17):13870-13883. doi: 10.18632/oncotarget.24493. eCollection 2018 Mar 02. PMID: 29568401; PMCID: PMC5862622.
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Oncotarget. 2018 Feb 14;9(17):13870-13883. doi: 10.18632/oncotarget.24493. eCollection 2018 Mar 02.

A single digital droplet PCR assay to detect multiple .

Oncotarget

Pieter A Boonstra, Arja Ter Elst, Marco Tibbesma, Lisette J Bosman, Ron Mathijssen, Florence Atrafi, Frits van Coevorden, Neeltje Steeghs, Sheima Farag, Hans Gelderblom, Winette T A van der Graaf, Ingrid M E Desar, Jacqueline Maier, Jelle Overbosch, Albert J H Suurmeijer, Jourik Gietema, Ed Schuuring, Anna K L Reyners

Affiliations

  1. University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Groningen 9713 GZ, The Netherlands.
  2. University of Groningen, University Medical Center Groningen, Department of Pathology, Groningen 9713 GZ, The Netherlands.
  3. Department of Medical Oncology, Erasmus University Medical Center Rotterdam, Rotterdam 3015 CE, The Netherlands.
  4. Antoni van Leeuwenhoek, Netherlands Cancer Institute, Department of Surgery, Amsterdam 1066 CX, The Netherlands.
  5. Antoni van Leeuwenhoek, Netherlands Cancer Institute, Department of Medical Oncology, Amsterdam 1066 CX, The Netherlands.
  6. Leiden University Medical Center, Department of Medical Oncology, Leiden 2300 RC, The Netherlands.
  7. Radboud University Medical Center, Department of Medical Oncology, Nijmegen 6500 HB, The Netherlands.
  8. University of Leipzig, Center for Internal Medicine, Department of Hematology/Oncology, Leipzig 04103, Germany.
  9. University of Groningen, University Medical Center Groningen, Department of Radiology, Groningen 9713 GZ, The Netherlands.

PMID: 29568401 PMCID: PMC5862622 DOI: 10.18632/oncotarget.24493

Abstract

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are characterized by oncogenic

METHODS: A ddPCR assay was designed using two probes that cover both hotspots. Available archival FFPE tumor tissue from 27 consecutive patients with known KIT exon 11 mutations and 9 randomly selected patients without exon 11 mutations were tested. Plasma samples were prospectively collected in a multicenter bio-databank from December 2014. ctDNA was analyzed of 22 patients with an exon 11 mutation and a baseline plasma sample.

RESULTS: The ddPCR assay detected the exon 11 mutation in 21 of 22 tumors with exon 11 mutations covered by the assay. Mutations in ctDNA were detected at baseline in 13 of 14 metastasized patients, but in only 1 of 8 patients with localized disease. In serial plasma samples from 11 patients with metastasized GIST, a decrease in mutant droplets was detected during treatment. According to RECIST 1.1, 10 patients had radiological treatment response and one patient stable disease.

CONCLUSION: A single ddPCR assay for the detection of multiple exon 11 mutations in ctDNA is a feasible, promising tool for monitoring treatment response in patients with metastasized GIST and should be further evaluated in a larger cohort.

Keywords: GIST; cell-free circulating DNA; digital droplet PCR; plasma; single assay

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

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