Abstract 625: Co-amplification of CDK4 and MDM2 plus HMGA2 fusion in a patient with myogenic differentiation dedifferentiated liposarcoma
Authors: Huang Gang , Li Xianan , Wang Chunyang , He Qifan , Wang Xiaojuan 
Published: July 2021

BACKGROUND: Dedifferentiated liposarcoma (DDLPS) with myogenic differentiation is a rare subtype of soft tissue sarcoma, and its pathogenesis remains unclear. The morphological resemblance with myofibroblastic sarcoma and rhabdomyosarcoma may easily result in misdiagnosis. Some studies have shown that myogenic differentiation is considered as a poor prognostic factor for DDLPS; consequently, it is of great clinical significance for its accurate diagnosis. Next-generation sequencing (NGS) can be performed to better explore the molecular characteristics and targeted therapies of myogenic differentiation DDLPS. Here, we reported a rare case of myogenic differentiation DDLPS harboring co-amplification of CDK4 and MDM2 plus HMGA2 gene fusion, which was clarified via NGS.

CASE PRESENTATION: A 61-year-old male patient presented with local soft tissue thickening in the right groin and scrotum by PET-CT. Pathological examination revealed a 5.8*4.5*3.5cm mass in the right groin with an enveloping appearance and gray-brown section. Microscopic examination showed the parenchymal mass was composed of spindle cells. Immunohistochemistry (IHC) reported that spindle cells were diffusely positive for desmin and vimentin; focally positive for epithelial membrane antigen, smooth muscle actin and actin; and negative for ALK, S-100, myogenin, CD30, CK, h-caldesmon, MyoD1, STAT6, SOX-10 and β-catenin. The approximate Ki-67 label index was 40%. Combining with the morphology and IHC, the patient was diagnosed with myogenic differentiated soft tissue sarcoma. After surgical resection, NGS was performed on resected tissues to further identify the subtype due to its high aggressiveness. Fresh surgical tissues were tested by the NGS-based 825-gene DNA panel and 395-gene RNA panel. The tumor samples contained three somatic mutations: ELAC2 p.H194R (14.4%), HRH2 p.S325F (18.1%), and KEL p.G167D (19.3%). Copy number analysis revealed copy number gains for CDK4, MDM2 and IGF1R in the patient. He also carried HMGA2(E3)-CCDC91(E2), FRS2(E3)-BCAT1(E3) and ATG5(E5)-DSG3(E13) gene fusion. CDK4 and MDM2 gene amplification is the clinical diagnostic marker of DDLPS, this patient was finally diagnosed as DDLPS with myogenic differentiation. Additionally, HMGA2 gene fusion was firstly reported in myogenic differentiation DDLPS, which was often discussed in lipoma before.

CONCLUSION: To date, limited scientific literature is available for a comprehensive understanding of the genetic characteristics of myogenic differentiation DDLPS. For the first time, we reported a case of myogenic differentiation DDLPS with simultaneous CDK4, MDM2 amplification and HMGA2 gene fusion, which may be the potential tumorigenic mechanism of myogenic differentiation DDLPS.

Citation Format: Gang Huang, Xianan Li, Chunyang Wang, Qifan He, Xiaojuan Wang. Co-amplification of CDK4 and MDM2 plus HMGA2 fusion in a patient with myogenic differentiation dedifferentiated liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 625.