The presence NTRK gene fusions is one of the eligibility requirements for the recently FDA-approved therapy Vitrakvi (larotrectinib), a therapy indicated in adult and pediatric patients with solid tumors regardless of the type of tumor. NTRK gene fusions have been described in many cancers at various frequencies, including common cancers such as lung, thyroid, and colorectal cancers.
Testing Specific for the Assessment of NTRK Gene Fusions:
- NTRK Gene Fusion Panel (Mayo ID: NTRK): This targeted panel provides NGS sequencing of the NTRK genes – NTRK1, NTRK2, and NTRK3. This method is designed to detect the most common NTRK fusions as well as similar NTRK fusions involving novel fusion partners.
- Tropomyosin Receptor Kinase (TRK) Immunostain, Technical Component Only (Mayo ID: TRK): IHC staining with a pan-TRK antibody detects proteins TRKA, TRKB, and TRKC which are encoded by NTRK1, NTRK2, and NTRK3.
Testing Designed for Specific Tumor Types:
- ETV6 (12p13.2) Rearrangement, FISH, Tissue (Mayo ID: ETV6F): In specific diseases, such as infantile fibrosarcoma, where the predominant abnormality and gene fusion partner is known, FISH testing is a reliable method for detecting NTRK gene fusions. In the case of infantile fibrosarcoma, mammary analogue secretory carcinoma, and secretory carcinoma of the breast, the NTRK3-ETV6 gene fusion is the predominant driver mutation.
- Lung Cancer NGS Panel with Rearrangements (Mayo ID: LNGPR): The lung cancer specific NGS panel assesses for mutation in eight genes and rearrangements (fusions) in four genes including NTRK1 which is the most commonly described NTRK gene fusion in lung cancer.
- Neuro-Oncology Expanded NGS Panel with Rearrangement, Tumor (Mayo ID: NONCP): The neuro-oncology specific NGS panel assesses for mutations in 150 genes and rearrangements (fusions) in 81 genes including NTRK1, NTRK2, and NTRK3.
At MCL, this testing can be performed concurrently with other tissue testing such as the gastrointestinal stromal tumor NGS panel (GISTP), colorectal RAS/RAF NGS panel (RASFP), or it can be performed as a stand-alone assay on any FFPE tumor tissue.