Biomarker NTRK Coverage from Every Angle

Gene Fusion Testing Strategies for Colorectal, Skin, and Lung Cancers

By: Julia Fiederlein
Posted: Wednesday, October 27, 2021

The low prevalence of gene fusions across common malignancies poses challenges in the era of precision medicine, according to Caterina Marchiò, MD, PhD, of the Candiolo Cancer Institute, Italy, and colleagues; thus, there is a need for a feasible and sensitive diagnostic process. Using a comprehensive method, an analysis published in the journal Cancers provided real-world data on the enrichment of gene fusions in colorectal carcinomas, melanomas, and lung adenocarcinomas characterized by the absence of mutations in the main driver genes as well as in colorectal tumors with microsatellite instability.

“By demonstrating this enrichment in a ‘real-world’ cohort, we confirm the feasibility of this approach, suggesting a workflow applicable in diagnostic practice,” the investigators commented. “We [also] provide comparative data across in situ methods and in vitro nucleic acid–based assays to document effective NTRK gene fusion detection.”

The investigators performed RNA-based targeted next-generation sequencing on 125 samples from patients with colorectal carcinoma, melanoma, or lung adenocarcinoma lacking genetic alterations in canonical driver genes or with a colorectal carcinoma harboring a microsatellite instability phenotype. The gene fusion rates were compared with in silico data from the Memorial Sloan Kettering Cancer Center. Multitarget quantitative reverse transcription polymerase chain reaction and pan-TRK immunohistochemistry were used for NTRK gene fusion detection.

Gene fusions were detected in 12.7% of microsatellite-instable colorectal carcinomas and in 5.7% of “gene driver–free” tumors (melanomas: 10.7%; lung adenocarcinomas: 8.3%); according to the investigators, these rates seemed to be significantly higher than those reported in the microsatellite stable and “gene driver–positive” Memorial Sloan Kettering Cancer Center cohorts. The sensitivity of pan-TRK immunohistochemistry was 100%, and the specificity was 91.7%; there seemed to be heterogeneous and/or subtle staining patterns.

“The heterogeneous expression in NTRK fusion–positive tumors unveils challenging patterns to recognize and raises questions on the effective translation of the chimeric protein,” the investigators concluded.

Disclosure: For full disclosures of the study authors, visit

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