Detection of KIT and PDGFRA mutations in the plasma of patients with gastrointestinal stromal tumor

Targeted Oncology
Guhyun KangKyoung-Mee Kim

Abstract

In subsets of gastrointestinal stromal tumors (GISTs), mutations of the KIT and PDGFRA receptor tyrosine kinases correlate with tumor prognosis and response to tyrosine kinase inhibitors (TKIs). Determining genotypes in TKI-resistant GISTs is challenging due to the potential risks and limitations of repeated biopsies during the course of treatment. We prospectively collected plasma samples from three GIST patients harboring KIT mutations that were detected in tissue DNA. The plasma samples were then analyzed for mutations in KIT, PDGFRA, and BRAF via next-generation sequencing. We were able to identify primary KIT mutations in all plasma samples. Additional mutations, including KIT exon 17 S821F and PDGFRA exon 18 D842V, were detected in the patient-matched plasma samples during follow-up and appeared to result in decreased sensitivity to TKIs. Our results demonstrate an approach by which primary and secondary mutations are readily detected in blood-derived circulating tumor DNA from patients with GIST. These mutations can be used as biomarkers for prediction of treatment response. The identification of a resistance mutation in plasma DNA will allow early change to alternative TKIs or dose escalation of imatinib for optimal pat...Continue Reading

References

Sep 7, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael C HeinrichJonathan A Fletcher
Mar 24, 2009·Lancet·Ronald P DeMatteoAmerican College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team
May 18, 2010·Journal of the National Comprehensive Cancer Network : JNCCN·George D DemetriJeffrey D Wayne
Nov 18, 2011·Nature Reviews. Cancer·Christopher L CorlessMichael C Heinrich
May 3, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrea L Richardson, J Dirk Iglehart
Jul 9, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jacqueline MaierNikolas von Bubnoff
Jul 10, 2013·Nature Reviews. Clinical Oncology·Emily CrowleyAlberto Bardelli
Sep 26, 2013·International Journal of Molecular Sciences·Yahya I ElshimaliJaydutt V Vadgama

Citations

Nov 12, 2015·Thoracic Cancer·Hongwei GuoJian Zhang
May 15, 2016·Molecular Diagnosis & Therapy·Guhyun KangKyoung-Mee Kim
Mar 19, 2019·International Journal of Cancer. Journal International Du Cancer·Stefanie JilgNikolas von Bubnoff
Jul 14, 2018·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·X Liu, K-M Chu
Mar 12, 2019·Therapeutic Advances in Medical Oncology·Gloria RavegniniSabrina Angelini
Mar 28, 2019·Current Cancer Drug Targets·Yu Wang, Jerry Call
Mar 1, 2021·Current Treatment Options in Oncology·David Gómez-PeregrinaCésar Serrano

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Cell Signaling by Tyrosine Kinases

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