Abstract 171P
Background
NTRK1, NTRK2 and NTRK3 rearrangements are rare genetic events, which are difficult to detect due to diversity of translocation partners and varying position of break-points.
Methods
We assumed that the fusion-driven activation of the NTRK1/2/3 results in the overexpression of the kinase portion of the involved gene, and developed a PCR assay which evaluates the ratio between 5’- and 3’- ends of the NTRK1, NTRK2 and NTRK3 transcripts in the tumor cDNA. The identity of translocation variants in tumors with unbalanced 5’/3’-end expression was established by allele-specific PCR tests or next-generation sequencing (NGS).
Results
NTRK1/2/3 rearrangements were detected in 6/5102 (0.12%) consecutive non-small cell lung carcinomas (NSCLCs). All these NTRK fusions were represented by distinct variants and were present in patients of distinct gender and age (FAM118Bex8/NTRK1ex9: m, 64 y; SQSTM1ex5/NTRK1ex9: f, 64 y; TPM3ex8/NTRK1ex10: f, 60 y; CD74ex6/NTRK1ex10: f, 47 y; SQSTM1ex4/NTRK2ex14: m, 79 y; ETV6ex5/NTRK3ex15: m, 58 y). In contrast to low frequency in NSCLCs, there was a noticeable occurrence of NTRK1/2/3 rearrangements in pediatric tumors (9/93, 9.7%), salivary gland carcinomas (3/85, 3.5%) and microsatellite-unstable colorectal cancers (3/33, 9.1%). While there was a diversity of the translocation variants in NSCLCs, more than a half of NTRK fusions detected in non-NSCLC tumors were represented by the ETV6ex5/NTRK3ex15 chimera.
Conclusions
PCR test for 5’/3’-end unbalanced expression is a cost-efficient screening tool for NTRK1/2/3 rearrangements.
Legal entity responsible for the study
The authors.
Funding
Russian Science Foundation, grant 17-75-30027.
Disclosure
All authors have declared no conflicts of interest.