In:
Pediatric Blood & Cancer, Wiley, Vol. 67, No. 5 ( 2020-05)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1545-5009
,
1545-5017
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2020
ZDB Id:
2130978-4
