The Lung NGS Fusion Profile is an RNA-based next-generation sequencing panel that detects translocations and fusions of the genes ALK, NTRK1, NTRK2, NTRK3, RET and ROS1 with known and novel fusion partners. Point mutations in select exons of these six genes are also detected. Examples of some of the published fusions detectable in this test include EML4-ALK, KIF5B-ALK, NPM1-ALK, CD74-NTRK1, MPRIP-NTRK1, TPM3-NTRK1, TRIM24-NTRK2, PAN3-NTRK2, ETV6-NTRK3, CCD6-RET (aka RET-PTC1), KIF5B-RET, NCOA4-RET (aka RET-PTC3), CD74-ROS1, SLC34A2-ROS1, and TPM3-ROS1.
This test may be used to select patients for therapy with the FDA-approved TRK inhibitor Vitrakvi® (larotrectinib).
We recommend FISH as the primary method of ALK, RET, and ROS1 rearrangement detection. We suggest using this test for NTRK analysis and/or cases that fail to provide conclusive FISH results. See also NTRK NGS Fusion Profile and NTRK & RET NGS Fusion Profile.
Fusions of the ALK, NTRK1, NTRK2, NTRK3, RET and ROS1 kinase genes with various partner genes have been reported as oncogenic drivers in multiple cancer types including lung adenocarcinoma. Chimeric proteins resulting from the gene fusions may be overexpressed or constitutively activated and lead to progression of cancer. Patients whose tumors have such gene fusions may respond to various kinase inhibitors. In non-small cell lung carcinoma (NSCLC), these gene fusions are detected with the following approximate frequencies: ALK (4-6%), NTRK (1%), RET (1-2%), and ROS1 (1-2%).
FFPE tissue: Paraffin block is preferred. Alternatively, send 1 H&E slide plus 5-10 unstained slides cut at 5 or more microns. Please use positively-charged slides and 10% NBF fixative. Do not use zinc fixatives.
Use cold pack for transport. Make sure cold pack is not in direct contact with specimen.