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Identification of NTRK Fusions in Solid Tumors: Focus on Local Testing Approaches

By: Lauren Harrison, MS
Posted: Tuesday, February 22, 2022

A recent study found that the most common method of testing for NTRK gene fusions was with RNA-based next-generation sequencing. This approach was able to identify many different NTRK fusions, and the majority of NTRK fusions occurred at a low frequency among multiple tumor types. Theodore W. Laetsch, MD, of the Children’s Hospital of Pennsylvania in Philadelphia, and colleagues published these findings in Cancer Genetics.

This study pooled information from 3 clinical trials of the selective TRK inhibitor larotrectinib and analyzed information from 225 patients with 19 different solid tumors. Researchers looked at both the molecular pathology reports and applied testing methods from each of these studies. The characteristics of detected fusions in different tumor types were also reported.

The most common method of detecting NTRK gene fusions was next-generation sequencing (87%), and RNA sequencing was used more commonly (43%) than DNA sequencing (24%) or DNA/RNA sequencing (20%). Fluorescence in situ hybridization (6%) and polymerase chain reaction (5%) were used in tumor types where NTRK fusions were shown to be highly recurrent molecular changes, and they were the sole method of NTRK fusion detection in many infantile fibrosarcoma and secretory breast cancer cases. 

NTRK3 gene fusions were most commonly identified across all tumor types, with 48% of the 225 tumor samples harboring these mutations. NTRK1 gene fusions were noted in 39% of tumors, and NTRK2 gene fusions were present in 13%. There were 54 different fusion partners identified in this cohort, and 72% of them were identified in a single tumor alone. The most common gene fusions in this group were ETV6 and NTRK3 (41% of tumors). It was reported in all salivary gland, breast, gastrointestinal stromal, and congenital mesoblastic tumors.

“This pattern of occurrence supports the need for validated and appropriate routine biomarker testing methods that provide complete coverage for all three NTRK genes regardless of partners and breakpoints,” concluded the authors.

Disclosure: For a full list of authors’ disclosures, visit

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