A 71-year-old male was diagnosed with colorectal carcinoma of the ascending colon. Mutation testing revealed wild-type KRAS, NRAS and BRAF.
NTRK gene fusion testing
Subsequent IHC screening was positive for TRKA, TRKB, and TRKC.
Figure 21: Pan-TRK IHC of Patient with Colon Adenocarcinoma
A DNA-only NGS (Foundation OneTM assay) was used to confirm the rearrangement. MTOR (A469T) and TP53 (R175H) mutations were detected, but no copy number variants were identified. The NTRK1-TPM3 fusion was detected.
FISH was used as a final confirmatory approach.
Figure 22: FISH of Patient with Colon Adenocarcinoma
TRK inhibitor treatment
The patient was treated with a TRK inhibitor as first-line treatment.
Clinical interpretation and impact of NTRK gene fusion testing
This case demonstrates that NTRK-rearranged colorectal carcinomas are usually right-sided and RAS-BRAF wild-type. The fusion can be detected by DNA-only NGS, but there is a greater risk of false-negative results. In addition, FISH could be useful for histologies with a very high rate of NTRK rearrangement, when the RNA part of the NGS fails, or if there is insufficient input material for NGS.