Gene rearrangements in consecutive series of pediatric inflammatory myofibroblastic tumors

Pediatr Blood Cancer. 2020 May;67(5):e28220. doi: 10.1002/pbc.28220. Epub 2020 Feb 16.


Background: Inflammatory myofibroblastic tumors (IMTs) are exceptionally rare neoplasms, which are often driven by rearranged tyrosine kinases.

Methods: This study considered 33 consecutive patients with IMT (median age, 6.6; age range, 0.6-15.8 years). RNA and cDNA were successfully obtained in 29 cases. The molecular analysis included sequential tests for 5'/3'-end unbalanced gene expression, variant-specific PCR, and next-generation sequencing (NGS).

Results: 5'/3'-end unbalanced ALK expression was revealed in 15/29 (52%) IMTs. Strikingly, all these tumors demonstrated high amount of ALK protein detected by immunohistochemistry. Variant-specific PCR was capable of identifying the type of ALK rearrangement in 11/15 IMTs with 5'/3'-end unbalanced ALK expression. The remaining four tumors were analyzed by NGS; two known and two novel (CLTC-ins6del84-ALK and EEF1G-ALK) ALK rearrangements were detected. Five IMTs demonstrated 5'/3'-end unbalanced ROS1 expression, and all these tumors carried TFG-ROS1 fusion. Nine tumors, which were negative for 5'/3'-end unbalanced ALK/ROS1 expression, were subjected to further analysis. Variant-specific PCR revealed two additional tumors with gene rearrangements (TFG-ROS1 and ETV6-NTRK3). The remaining seven IMTs were tested by NGS; single instances of TFG-ROS1 and novel SRF-PDGFRb translocations were detected.

Conclusions: Twenty-four of 29 IMTs (83%) were shown to have druggable rearrangements involving tyrosine kinases, 20 of these 24 gene fusions were detectable by simple and inexpensive PCR assay, which is based on the detection 5'/3'-end unbalanced gene expression.

Keywords: IHC; IMT; NGS; PCR; fusion; tyrosine kinases.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Rearrangement*
  • Humans
  • Infant
  • Male
  • Neoplasms / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Polymerase Chain Reaction*


  • Oncogene Proteins, Fusion