Detecting Secondary C-KIT Mutations in the Peripheral Blood of Patients with Imatinib-Resistant Gastrointestinal Stromal Tumor

Oncology
Noriko WadaYuichiro Doki

Abstract

Imatinib is a standard treatment for metastatic gastrointestinal stromal tumor (GIST). Imatinib resistance is mostly caused by secondary mutations in C-KIT. The antitumor effect of second-line agents is correlated with the type of secondary mutation: indeed, sunitinib is effective against tumors with C-KIT exon 13 or 14 mutations. We investigated whether secondary C-KIT mutations can be detected in circulating tumor DNA (ctDNA) from peripheral blood. This study included 4 patients who underwent resection of imatinib-resistant GIST. Tumor-specific mutations in each tumor were determined by Sanger sequencing. ctDNA was extracted from peripheral blood obtained before and after the treatment of imatinib-resistant lesions. Each of the secondary target mutations in ctDNA was investigated, using a next-generation sequencer. Imatinib-resistant lesions had single-nucleotide substitutions in C-KIT exon 13 in 3 patients and exon 18 in 1 patient. Identical secondary C-KIT mutations could be detected in ctDNA with a mutant fraction range of 0.010-9.385%. One patient had growth of an imatinib-resistant tumor containing a C-KIT exon 13 mutation, and the fraction of ctDNA decreased after initiation of sunitinib. Detection of secondary C-KIT mu...Continue Reading

Citations

Mar 21, 2017·Expert Review of Molecular Diagnostics·Amber E BannonMichael C Heinrich
Mar 19, 2019·International Journal of Cancer. Journal International Du Cancer·Stefanie JilgNikolas von Bubnoff
Feb 6, 2020·Oncotarget·Rabih SaidApostolia M Tsimberidou
Oct 6, 2018·Journal of Diabetes and Metabolic Disorders·Fatemeh Khatami, Seyed Mohammad Tavangar
Jun 18, 2020·Cancer Management and Research·Fangxing Peng, Yao Liu
Mar 12, 2019·Therapeutic Advances in Medical Oncology·Gloria RavegniniSabrina Angelini
Mar 28, 2019·Current Cancer Drug Targets·Yu Wang, Jerry Call
Nov 11, 2019·Molecular Aspects of Medicine·Heidi Maria NamløsLeonardo A Meza-Zepeda
Mar 1, 2021·Current Treatment Options in Oncology·David Gómez-PeregrinaCésar Serrano
Aug 14, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M L HemmingS George

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Sequencing

Several sequencing approaches are employed to understand and examine tumor development and progression. These include whole genome as well as RNA sequencing. Here is the latest research on cancer sequencing.