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South Korean Study on Detection of NTRK Fusions Using Next-Generation Sequencing

By: Lauren Harrison, MS
Posted: Thursday, May 12, 2022

A group of researchers in South Korea found that RNA-based next-generation sequencing assays can detect NTRK fusions and may be used to characterize fusion transcripts. Yoon La Choi, MD, of Samsung Medical Center and Sungkyunkwan University School of Medicine, Seoul, and colleagues published their findings from multiple centers in Cancer Research and Treatment.

The researchers validated the presence of TRK in 18 tumor samples using the VENTANA pan-TRK assay, including a positive standard reference, 8 positive clinical samples, and 9 negative clinical samples. These samples were surgical specimens from six different types of cancer: colorectal adenocarcinoma, inflammatory myofibroblastic tumor of the lung, secretory salivary gland tumor, glioblastoma, prostate stromal sarcoma, and mucinous adenocarcinoma. These samples were then tested using three RNA next-generation sequencing panels (TruSight Oncology 500, Lung Cancer Panel v3.0, and Oncomine Comprehensive Assay) and one DNA next-generation sequencing panel (Oncopanel v.4.3) to detect NTRK gene fusions. These panels were run at six unique institutions in South Korea.

No NTRK fusion reads were noted in any of the NTRK fusion–negative samples, correlating to a 100% specificity at all the institutions for all the assays. In contrast, the sensitivity of NTRK fusion detection was different among the institutions. Two of the RNA-based next-generation sequencing assays had 100% sensitivity of detecting the NTRK-positive samples at two of the hospitals. However, one of these RNA-based assays had an 87.5% sensitivity at a different institution. Notably, the DNA-based assay showed a 37.5% clinical sensitivity. All of the assays had a 100% analytical sensitivity.

False-negative results occurred due to low tumor purity (20%) and poor RNA quality, according to the study authors. Additionally, the DNA-based sequencing panel produced more false-negative results than the RNA panels, leading researchers to believe that RNA-based sequencing has a high success rate in detecting NTRK fusions.

Disclosure: The study authors reported no conflicts of interest.


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