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UK Genomes Project: Are NTRK Gene Fusions Actionable Biomarkers?

By: Vanessa A. Carter, BS
Posted: Sunday, August 1, 2021

John Bridgewater, PhD, of the UCL Cancer Institute, London, United Kingdom, and colleagues examined the overall survival of patients with NTRK gene fusions compared with those without it. Their findings, which were presented during the virtual edition of the American Association for Cancer Research (AACR) Annual Meeting 2021, demonstrated no statistical difference in overall survival—although patients with NTRK gene fusions tended to have a higher risk of death than those without (Abstract 394).

“Co-occurrence of NTRK fusions and other biomarkers was rare, except for high tumor mutation burden and high microsatellite instability in colorectal cancer,” concluded the researchers. “These results highlight NTRK fusions as actionable biomarkers and emphasize the need for NTRK gene fusion testing.”

This retrospective study analyzed the data of 15,223 patients from the 100,000 Genomes Project and various UK cancer databases who underwent tumor whole-genome sequencing. Along with NTRK gene fusions, the investigators evaluated key alterations in oncogenic drivers such as ROS1, HER2, ALK, KRAS, BRAF, and EGFR; microsatellite instability; and tumor mutation burden.

NTRK fusions were identified in 38 patients (0.2%) across 11 types of cancer, the most common being colorectal cancer (n = 9), breast cancer (n = 9), and sarcoma (n = 7). There appeared to be no significant difference in overall survival between patients with and without NTRK gene fusions, and the hazard ratio was 1.47.

Among the examined oncogenic drivers, a KRAS mutation was found in just two patients with NTRK fusion who had hepatobiliary cancer; the oncogenic driver frequency for individuals without gene fusions fluctuated from 0.1 to 11.6%. Of note, patients with colorectal cancer who had NTRK fusions had a higher tumor mutation burden (21% vs. 6%) and microsatellite instability (18% vs. 6%) than individuals without them.

Disclosure: For full disclosures of the study authors, visit abstractsonline.com.



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