Kinase genotype analysis of gastric gastrointestinal stromal tumor cytology samples using targeted next-generation sequencing

Ferga C. Gleeson, Benjamin R. Kipp, Sarah E. Kerr, Jesse S. Voss, Rondell Graham, Michael B. Campion, Douglas M. Minot, Zheng J. Tu, Eric W Klee, Konstantinos N Lazaridis, Michael R. Henry, Michael J. Levy

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Gastric gastrointestinal stromal tumors (GISTs) usually contain the mast/stem cell growth factor receptor Kit gene (KIT) or platelet-derived growth factor receptor A (PDGFRA) mutations that can be targeted by, or mediate resistance to, imatinib. Diagnostic material often is obtained by endoscopic ultrasound-guided fine-needle aspiration, which often is unsuitable for molecular analysis. We investigated whether targeted next-generation sequencing (NGS) can be used in multiplex genotype analysis of cytology samples collected by endoscopic ultrasound-guided fine-needle aspiration. We used the Ion AmpliSeq V2 Cancer Hotspot NGS Panel (Life Technologies, Carlsbad, CA) to identify mutations in more than 2800 exons from 50 cancer-associated genes in GIST samples from 20 patients. We identified KIT mutations in 58% of samples (91% in exon 11 and 9% in exon 17) and PDGFRA mutations in 26% (60% in exon 18 and 40% in exon 12); 16% of samples had no mutations in KIT or PDGFRA. No pathogenic alterations were found in PIK3CA, BRAF, KRAS, NRAS, or FGFR3. We predicted that 32% of patients would have primary resistance to imatinib, based on mutations in exon 17 of KIT, exon 18 of PDGFRA (D842V), or no mutation in either gene. Targeted NGS of cytology samples from GISTs is feasible and provides clinically relevant data about kinase genotypes that can help guide individualized therapy.

Original languageEnglish (US)
Pages (from-to)202-206
Number of pages5
JournalClinical Gastroenterology and Hepatology
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2015

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Gastrointestinal Stromal Tumors
Cell Biology
Exons
Stomach
Phosphotransferases
Platelet-Derived Growth Factor Receptors
Genotype
Mutation
Endoscopic Ultrasound-Guided Fine Needle Aspiration
Proto-Oncogene Proteins c-kit
Stem Cell Factor
Growth Factor Receptors
Neoplasm Genes
Genes
Ions
Technology

Keywords

  • EUS-FNA
  • Molecular genetics
  • Personalized medicine
  • Targeted therapy
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Kinase genotype analysis of gastric gastrointestinal stromal tumor cytology samples using targeted next-generation sequencing. / Gleeson, Ferga C.; Kipp, Benjamin R.; Kerr, Sarah E.; Voss, Jesse S.; Graham, Rondell; Campion, Michael B.; Minot, Douglas M.; Tu, Zheng J.; Klee, Eric W; Lazaridis, Konstantinos N; Henry, Michael R.; Levy, Michael J.

In: Clinical Gastroenterology and Hepatology, Vol. 13, No. 1, 01.01.2015, p. 202-206.

Research output: Contribution to journalArticle

Gleeson, Ferga C. ; Kipp, Benjamin R. ; Kerr, Sarah E. ; Voss, Jesse S. ; Graham, Rondell ; Campion, Michael B. ; Minot, Douglas M. ; Tu, Zheng J. ; Klee, Eric W ; Lazaridis, Konstantinos N ; Henry, Michael R. ; Levy, Michael J. / Kinase genotype analysis of gastric gastrointestinal stromal tumor cytology samples using targeted next-generation sequencing. In: Clinical Gastroenterology and Hepatology. 2015 ; Vol. 13, No. 1. pp. 202-206.
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AU - Minot, Douglas M.

AU - Tu, Zheng J.

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AU - Levy, Michael J.

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