PURPOSE

Neurotrophic tyrosine receptor kinase (NTRK) fusions have been described as oncogenic drivers in a variety of tumors. However, little is known about the overall frequency of NTRK fusion in unselected pediatric tumors. Here, we assessed the frequency, fusion partners, and clinical course in pediatric patients with NTRK fusion-positive tumors.

PATIENTS AND METHODS

We studied 1,347 consecutive pediatric tumors from 1,217 patients who underwent tumor genomic profiling using custom-designed DNA and RNA next-generation sequencing panels. NTRK fusions identified were orthogonally confirmed.

RESULTS AND DISCUSSION

NTRK fusions were identified in 29 tumors from 27 patients with a positive yield of 2.22% for all patients and 3.08% for solid tumors. Although fusions were found exclusively in CNS tumors and fusions were highly enriched in papillary thyroid carcinomas, fusions were identified in all tumor categories. The most canonical fusion was observed in 10 patients with diverse types of tumors. Several novel NTRK fusions were observed in rare tumor types, including in ganglioglioma and in papillary thyroid carcinomas. The detection of an NTRK fusion confirmed the morphologic diagnosis including five cases where the final tumor diagnosis was largely based on the discovery of an NTRK fusion. In one patient, the diagnosis was changed because of the identification of an fusion. One patient with infantile fibrosarcoma was treated with larotrectinib and achieved complete pathologic remission.

CONCLUSION

NTRK fusions are more frequently seen in pediatric tumors than in adult tumors and involve a broader panel of fusion partners and a wider range of tumors than previously recognized. These results highlight the importance of screening for NTRK fusions as part of the tumor genomic profiling for patients with pediatric cancer.