Rhabdomyosarcoma With Epithelioid Features And NSD3:FOXO1 Fusion: Evidence For Reconsideration Of Previously Reported FOXO1:FGFR1 Fusion. (April 2023)

• Record Type: Journal Article
• Authors: Rakheja, Dinesh; Park, Jason Y.; Yang, Mary S.; Martinez, Diana P.; Koduru, Prasad; Wilson, Kathleen S.; Garcia, Rolando; Uddin, Naseem
• Is Part Of: International journal of surgical pathology. Volume 31:Number 2(2023)
• Page Start: 213
• Page End: 220
• Publication Date: 2023-04
• Subjects: epithelioid rhabdomyosarcoma -- rhabdomyosarcoma -- NSD3 -- FOXO1 -- FGFR1 -- gene fusion -- translocation -- amplification; Pathology, Surgical -- Periodicals; 617.07
• DOI: 10.1177/10668969221098084
• Languages: English
• ISSNs: 1066-8969

Abstract

Epithelioid rhabdomyosarcoma is a rare rhabdomyosarcoma variant for which no diagnostic recurrent driver genetic events have been identified. Here we report a rapidly progressive and widely metastatic rhabdomyosarcoma with epithelioid features that arose in the thigh of a male infant. Conventional cytogenetics revealed a t(8;13)(p11.2;q14) translocation. Fluorescence in situ hybridization studies showed rearrangement of FOXO1 and amplification of its 3" end, and rearrangement of NSD3 and amplification of its 5` end. Next generation sequencing identified a NSD3::FOXO1 fusion, which is a previously unreported gene fusion. We also review the historic report of a FOXO1::FGFR1 fusion in a solid variant of alveolar rhabdomyosarcoma and propose that NSD3::FOXO1 fusion may have been the more appropriate interpretation of the data presented in that report.