NTRK

NTRK abnormalities in NSCLC


TRK oncogene activation through the infusions involving an NTRK 1, NTRK 2 or NTRK3 are commonly observed in solid tumors including non-small cell lung cancer. These gene fusions in non-small cell lung cancer (NSCLC) occur with a frequency of about less than 1%.


NTRK gene fusions can occur in both squamous and non-squamous histology including neuroendocrine carcinomas. It is independent of sex and smoking status. They usually do not occur with other actionable driver mutations. There is seen with a slightly higher frequency in Asian patients.


DNA base sequencing shows an overall sensitivity and specificity of about 81% and 99.9% respectively for the detection of an TRK fusion compared to immunohistochemistry (IHC) which shows an overall sensitivity of 87.9% and specificity of 81%. RNA sequencing provides high sensitivity and specificity. A pattern-TRK IHC can be used as a screening test followed by a confirmatory NGS in positive cases.


Since lung cancer harbors these mutations at a lower frequency, as more recommendations are for screening with IHC first. Because TRK expression is normal and expected in certain organs such as the CNS, IHC positivity can be seen in cancers without TRK fusions. This can include tumors with neuroendocrine differentiation.


Plasma based, cell free DNA assays are not optimal for the detection of an TRK gene fusion.

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