Diagnostic testing approaches for the identification of patients with TRK fusion cancer prior to enrollment in clinical trials investigating larotrectinib

Erin R. Rudzinski, Jaclyn Hechtman, Sinchita Roy-Chowdhuri, Marion Rudolph, Christina M. Lockwood, Josh Silvertown, Justyna Wierzbinska, Kui Shen, Ricarda Norenberg, Hendrik Nogai, David S. Hong, Alexander Drilon, Theodore W. Laetsch

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: NTRK gene fusions are targetable oncogenic drivers independent of tumor type. Prevalence varies from highly recurrent in certain rare tumors to <1% in common cancers. The selective TRK inhibitor larotrectinib was shown to be highly active in adult and pediatric patients with tumors harboring NTRK gene fusions. Methods: We examined the techniques used by local sites to detect tumor NTRK gene fusions in patients enrolled in clinical trials of larotrectinib. We also report the characteristics of the detected fusions in different tumor types. Results: The analysis included 225 patients with 19 different tumor types. Testing methods used were next-generation sequencing (NGS) in 196 of 225 tumors (87%); this was RNA-based in 96 (43%); DNA-based in 53 (24%); DNA/RNA-based in 46 (20%) and unknown in 1 (<1%); FISH in 14 (6%) and PCR-based in 12 (5%). NanoString, Sanger sequencing and chromosome microarray were each utilized once (<1%). Fifty-four different fusion partners were identified, 39 (72%) of which were unique occurrences. Conclusions: The most common local testing approach was RNA-based NGS. Many different NTRK gene fusions were identified with most occurring at low frequency. This supports the need for validated and appropriate testing methodologies that work agnostic of fusion partners.

Original languageEnglish (US)
Pages (from-to)46-52
Number of pages7
JournalCancer Genetics
Volume260-261
DOIs
StatePublished - Jan 2022

Keywords

  • Gene fusion
  • Larotrectinib
  • Molecular diagnostic
  • Next-generation sequencing
  • NTRK

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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