Which patients to test for NTRK  gene fusions

Testing for NTRK gene fusions should be performed for patients with the following tumour types:

  • Tumour types known to frequently harbour NTRK gene fusions (i.e. infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analogue secretory carcinoma, and secretory breast cancer)1
  • Commonly diagnosed tumour types (e.g. lung cancer and colorectal cancer) known to be negative for other oncogenic alterations through exclusionary testing
  • CRC patients with MSI-H/dMMR status2-4
  • Thyroid cancer, salivary cancer, and sarcoma patients

Research has identified NTRK gene fusions in more than 2 dozen types of common and rare solid tumors5–8

NTRK gene fusions may be found across various adult and pediatric tumour types5–8

NTRK gene fusion frequency in adult cancers graphic NTRK gene fusion frequency in adult cancers graphic

Figure includes an example of tumour types which may harbour an NTRK gene fusion and is neither an all-inclusive list nor is it representative of all tumour types in which an NTRK gene fusion may present.

NTRK=neurotrophic tyrosine receptor kinase; TRK=tropomyosin receptor kinase; MSI-H=microsatellite instability-high; dMMR=mismatch repair deficient.

References: 1. Cocco E, et al. NTRK  fusion-positive cancers and TRK inhibitor therapy. Nature Reviews Clinical Oncology 2018;15: 731–47. 2. Pietrantonio F, et al. ALK, ROS1, and NTRK Rearrangements in Metastatic Colorectal Cancer. J Natl Cancer Inst 2017;109(12). 3. Chou A, et al. NTRK gene rearrangements are highly enriched in MLH1/PMS2 deficient, BRAF wild-type colorectal carcinomas—a study of 4569 cases. Mod Pathol 2019. https://doi.org/10.1038/s41379-019-0417-3. 4. Jiao X, et al. Co-occurrence of NTRK  fusions with other genomic biomarkers in cancer patients. ESMO 2019. Abstract no. 485P. 5. Vaishnavi A, et al. TRKing Down an Old Oncogene in a New Era of Targeted Therapy. Cancer Discov 2015;5(1):25-34. 6. Amatu A, et al. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open 2016;1:e000023. doi:10.1136/esmoopen-2015-000023 7. Okimoto RA, et al. Tracking down response and resistance to TRK inhibitors. Cancer Discov 2016;6(1):14-16. 8. Lange AM, et al. Inhibiting TRK proteins in clinical cancer therapy. Cancers 2018;10(4):E105. doi:10.3390/cancers10040105.