NTRK fusions in solid tumours: what every pathologist needs to know

Fusions involving the Neurotrophic tropomyosin receptor kinase (NTRK) gene family (NTRK1, NTRK2 and NTRK3) are targetable oncogenic alterations that are found in a diverse range of tumours. There is an increasing demand to identify tumours which harbour these fusions to enable treatment with selective tyrosine kinase inhibitors such as larotrectinib and entrectinib. NTRK fusions occur in a wide range of tumours including rare tumours such as infantile fibrosarcoma and secretory carcinomas of the salivary gland and breast, as well as at low frequencies in more common tumours including melanoma, colorectal, thyroid and lung carcinomas. Identifying NTRK fusions is a chal-lenging task given the different genetic mechanisms un-derlying NTRK fusions, their varying frequency across different tumour types, complicated by other factors such as tissue availability, optimal detection methods, accessi-bility and costs of testing methods. Pathologists play a key role in navigating through these complexities by deter-mining optimal approaches to NTRK testing which has important therapeutic and prognostic implications. This review provides an overview of tumours harbouring NTRK fusions, the importance of identifying these fusions, avail-able testing methods including advantages and limitations, and generalised and tumour-specific approaches to testing.

Automated summary

Fusions involving the NTRK gene family are targetable oncogenic alterations found in a diverse range of tumors. Identifying these fusions is challenging due to various genetic mechanisms, frequency differences, and other factors. Pathologists play a key role in determining optimal testing approaches with therapeutic and prognostic implications. This review provides an overview of tumors harboring NTRK fusions and available testing methods.