10171- MPC-16 SCREENING OF NTRK FUSION IN JAPANESE CENTRAL NERVOUS SYSTEM TUMORS

Abstract NTRK fusions have been reported to be rare in cancers across various organs, except for certain types of tumors. NTRK fusion positive tumors are reported to be highly sensitive to TRK inhibitors such as Larotrectinib and Entrectinib. It is very important to identify patients who may have benefit from these inhibitors. In central nerve system (CNS) tumors, especially gliomas, the frequency of NTRK fusions has been reported to be approximately 2%, however, the frequency of NTRK fusions in CNS tumors of Japanese patients is unknown. Pan-trk IHC is useful to identify NTRK fusion tumors, however, the physiological expression of trks in neural tissues hamper the identification of CNS tumors with NTRK fusion by IHC. In this study, we employed quantitative PCR (qPCR)-based screening system of NTRK fusions in CNS tumors by evaluating the imbalanced expression of NTRK1-3. We performed Real-time qPCR for NTRK1, NTRK2 and NTRK3 in 390 cases of Japanese CNS tumors. Primers and probes were designed to recognize each 5’-side and 3’-side of NTRK1-3. Cases with imbalanced expression for either NTRK1-3 were further analyzed using NanoString gene expression assay containing probes for each 5’-side and 3’-side of NTRK1-3. Cases showing imbalanced expression were sent for target RNA sequences. We found a glioblastoma (GB) case (1%) with CKD5RAP2(ex22)-NTRK2(ex14) in-frame fusion among 96 consecutive Japanese GBs, and another GB with BCR(ex1)-NTRK2(ex10) out-of-frame fusion. NTRK fusion positive rate of glioblastoma in this study was similar to that of previous studies (1.1-2.6%). Imbalanced gene expression-based screening was considered to be useful to detect NTRK fusion in CNS tumors.