Spectrum of kinase gene rearrangements in a large series of paediatric inflammatory myofibroblastic tumours

Abstract

IntroductionInflammatory myofibroblastic tumours (IMTs), being an exceptionally rare category of paediatric neoplasms, often contain druggable gene rearrangements involving tyrosine kinases.Methods and resultsThis 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.ConclusionsPCR‐based pipeline provides a highly efficient and non‐expensive alternative for molecular testing of IMTs. IMTs with no detectable rearrangements need further studies.