Only specific tests can uncover TRK fusion cancer

While NTRK gene fusions were one of the first oncogenes identified, they are not routinely tested for and/or included on all test platforms.1,2 TRK fusion cancer can be detected through a number of diagnostic tests; however, only sensitive and specific tests can reliably detect NTRK gene fusions.1,2

Next-generation sequencing (NGS) provides the most comprehensive view of a large number of genes and may identify NTRK gene fusions as well as other actionable alterations, with minimal tissue needed.3,4 However, it is important to know whether the NGS assay used for NTRK testing has the capacity to detect NTRK gene fusions.3,5

Commercial laboratories currently offering testing inclusive of NTRK1, NTRK2, and NTRK3

Immunohistochemistry (IHC) Pan-TRK IHC antibodies detect TRK proteins A,B,C, which may be expressed in both wild-type and fusion proteins. Protein expression may not be the result of a gene fusion event. There are currently only research-use antibodies.6

DNA fluorescence in situ hybridization (FISH) testing may have limited utility in uncovering NTRK gene fusions because it is not designed for multiplexing. In order to detect fusions at multiple locations, such as the 3 NTRK genes, multiple FISH tests would need to be run.7 Additionally, it can require a highly specialized pathology analysis.3-5,8

Reverse transcription polymerase chain reaction (RT-PCR) is designed to identify only known translocation partners and breakpoints and cannot identify novel breakpoints or novel fusion partners.9

testing

References: 1. Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov. 2015;5(1):25-34. 2. Kumar-Sinha C, Kalyana-Sundaram S, Chinnaiyan AM. Landscape of gene fusions in epithelial cancers: seq and ye shall find. Genome Med. 2015;7:129. doi:10.1186/s13073-015-0252-1. 3. Abel HJ, Al-Kateb H, Cottrell CE, et al. Detection of gene rearrangements in targeted clinical next-generation sequencing. J Mol Diagn. 2014;16(4):405-417. 4. Rogers T-M, Arnau GM, Ryland GL, et al. Multiplexed transcriptome analysis to detect ALK, ROS1 and RET rearrangements in lung cancer. Sci Rep. 2017;7:42259. doi:10.1038/srep42259. 5. Abel HJ, Duncavage EJ. Detection of structural DNA variation from next generation sequencing data: a review of informatic approaches. Cancer Genet. 2013;206(12):432-440. 6. Hechtman JF, Benayed R, Hyman DM, et al. Pan-trk immunohistochemistry is an efficient and reliable screen for the detection of NTRK fusions. Am J Surg Pathol. 2017;41(11):1547-1551. 7. Bourgeois JM, Knezevich SR, Mathers JA, Sorensen PHB. Molecular detection of the ETV6-NTRK3 gene fusion differentiates congenital fibrosarcoma from other childhood spindle cell tumors. Am J Surg Pathol. 2000;24(7):937-946. 8. Amatu A, Santore-Bianchi, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumor types. ESMO Open. 2016;1(2):e000023. 9. Abel H, Pfeifer J, Duncavage E. Translocation detection using next-generation sequencing. In: Kulkarni S, Pfeifer J, eds. Clinical Genomics. Amsterdam, Netherlands: Elsevier/Academic Press; 2015:151-164.

 

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