(P 122) ACTIONABLE FUSIONS IN DEDIFFERENTIATED LIPOSARCOMA: AN ANALYSIS OF 402 CASES IN THE AACR GENIE DATABASE

Objective: Dedifferentiated liposarcoma (DDLPS) are malignant mesenchymal neoplasms characterized by MDM2 amplification that occur predominantly in the retroperitoneal and are associated with significant morbimortality. Recurrent gene fusions have been described in DDLPS, but their specific frequency is not well established. Moreover, given DDLPS rarity, exploring public genomic databases can help investigate specific alterations in a higher number of patients.

Methods: We queried the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database Cohort v15.1-public to investigate the prevalence of currently Food and Drug Administration (FDA)-approved and other potentially actionable gene fusions in patients with dedifferentiated liposarcoma. Targets were identified by a literature review by the authors and included ALK, BRAF, EGFR, NRG1, NTRK, RET, and ROS1.

Results: We identified 420 samples of 402 patients diagnosed with DDLPS in the AAACR GENIE database v15.1-Public, of which 403 samples were profiled for structural variants. Most samples were derived from the primary tumor (65.7%), followed by metastasis (site unspecified; 19.3%), then local recurrence (12.1%). Median age was 64 years (range: 18 to >89) and 60.4% were males. The majority of samples harbored MDM2 (94.9%) and/or CDK4 (91.6%) amplifications. Actionable fusions were identified in 10 patients (2.5%). Fusions were identified in FGFR1 (n=3; 0.7%), NTRK1 (n=3; 0.7%), BRAF (n=1; 0.2%), FGFR3 (n=1; 0.2%), NTRK2 (n=1; 0.2%) and ROS1 (n=1; 0.2%). Most tumors (90%) that presented with actionable fusions also harbored MDM2 amplification.

Conclusion: Exploring a public large-scale genomic database, we identified that 2.5% of patients diagnosed with DDLPS could be eligible for treatments directed to actionable fusions. These actionable alterations were present in BRAF, FGFR, NTRK, and ROS1. Although patients with liposarcoma were initially excluded from guidelines regarding testing for actionable fusions for which agnostic drugs have been approved, our results corroborate recent data supporting testing patients diagnosed with DDLPS for actionable fusions, including those with MDM2 amplification.