Revisiting CDKN2A dysregulation in Ewing sarcoma

Ewing sarcoma (EwS) is a rare and aggressive malignancy, which frequently affects children. One of the few recurrent genomic variants in EwS is genomic copy number deletion of CDKN2A; however, the clinical consequences of dysregulation of CDKN2A in EwS are unclear. In this study, we revisit CDKN2A to investigate its role as a potential prognostic biomarker in EwS using data from EwS pre-clinical models as well as clinical samples from patients with EwS. We demonstrate the potential essentiality of CDKN2A dysregulation and sustained downstream CDK4/CCND1 activity. Finally, we present evidence that high expression of CDKN2A is a negative prognostic biomarker at diagnosis in EwS in three independent datasets. Our data may suggest that the role of CDKN2A may change across the clinical context of EwS, however, further study is necessary to validate the function of CDKN2A expression in EwS.