Molecular characteristics of dedifferentiated liposarcoma with broad rhabdomyosarcomatous differentiation.

Abstract

e23530 Background: Dedifferentiated liposarcoma (DDLPS) with broad rhabdomyosarcomatous differentiation has a worse prognosis compared with other types of DDLPS. Therefore, it is of importance to recognize its molecular characteristics in order to investigate individualized treatment strategies. Methods: We conduct next-generation sequencing (NGS) including DNA and RNA sequencing analysis in 5 DDLPS patients with broad rhabdomyosarcomatous differentiation and perform comparative analysis between well-differentiated and dedifferentiated components from the patients. Results: In the ten samples, several somatic copy-number variations (CNVs) including the gain of 12q are considered as frequent molecular alterations. IGFN1, FGFR4, BLM, RICTOR, RUNX1 and TOP1 mutation is the high-frequency single-nucleotide variations (SNVs). Novel BEST3/CD63/LGR5/CENPL-MDM2 and ERBB3-TAFA2 fusion genes are identified in this subtype of tumor. The comparative analysis between well-differentiated and dedifferentiated components recognized two categories of molecular variations: shared variations, such as FGFR4 and BLM mutation, ERBB3-TAFA2 fusion, and MYC amplification that are associated with tumorigenesis, and dedifferentiated-specific variations including GRIN2A, FOXP1 and TP53 mutation, CERS4-PTPRB and TRIO-TERT fusion, and ESR1 amplification, which are related with malignant progression. After surgery, the patient received adjuvant therapy. The mean follow-up of the patients was 30 months, and the mean recurrence-free survival (RFS) was 9.6 months. Conclusions: This NGS analysis disclosed the possible progression mechanisms and therapeutic targets in DDLPS with broad rhabdomyosarcomatous differentiation and provided insights contributing to the refinement of management in this tumor. [Table: see text]