Gene rearrangements in consecutive series of pediatric inflammatory myofibroblastic tumors.
Pediatr Blood Cancer
; 67(5): e28220, 2020 05.
Article
in En
| MEDLINE
| ID: mdl-32064735
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Rearrangement
/
Gene Expression Regulation, Neoplastic
/
Oncogene Proteins, Fusion
/
Polymerase Chain Reaction
/
Neoplasms
Type of study:
Clinical_trials
Limits:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Language:
En
Journal:
Pediatr Blood Cancer
Journal subject:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Year:
2020
Document type:
Article
Affiliation country:
RUSSIA