RESUMO
INTRODUCTION: Inflammatory myofibroblastic tumours (IMTs), being an exceptionally rare category of paediatric neoplasms, often contain druggable gene rearrangements involving tyrosine kinases. METHODS AND RESULTS: This study presents a large consecutive series of IMTs which were analysed for the presence of translocations by the PCR test for 5'/3'-end ALK, ROS1, RET, NTRK1, NTRK2 and NTRK3 unbalanced expression, variant-specific PCR for 47 common gene fusions and NGS TruSight RNA fusion panel. Kinase gene rearrangements were detected in 71 of 82 (87%) IMTs (ALK: n = 47; ROS1: n = 20; NTRK3: n = 3; PDGFRb: n = 1). The test for unbalanced expression had 100% reliability in identifying tumours with ALK fusions, but failed to reveal ROS1 rearrangements in eight of 20 (40%) ROS1-driven IMTs; however, ROS1 alterations were detectable by variant-specific PCR in 19 of 20 (95%) cases. ALK rearrangements were particularly common in patients below 1 year of age (10 of 11 (91%) versus 37 of 71 (52%), P = 0.039). ROS1 fusions occurred more often in lung IMTs than in tumours of other organs (14 of 35 (40%) versus six of 47 (13%), P = 0.007). Among 11 IMTs with no kinase gene rearrangement identified, one tumour demonstrated ALK activation via gene amplification and overexpression, and another neoplasm carried COL1A1::USP6 translocation. CONCLUSIONS: PCR-based pipeline provides a highly efficient and non-expensive alternative for molecular testing of IMTs. IMTs with no detectable rearrangements need further studies.