Abstract 1256: Validation of Ubiquitin specific peptidases 37 as a prognostic and diagnostic marker in osteosarcoma

Osteosarcoma has been a challenge for the oncologist because even after surgical removal of tumors 80 percent patients go on to develop metastasis to the Lung. Systematic development of Drug has been literally on a standstill in osteosarcoma. The emergence of Adjuvant therapy after surgery for localized osteosarcoma has increased the long term survival in patients under age 40 by 60 to 70 percent however for patients who go on to develop metastasis the prognosis is poor as there are limited therapeutic options. Protein ubiquitination and deubiquitylation plays an important role in controlling protein stability. Initial studies by us points to a model in which Ubiquitin specific peptidase 37 regulates cell cycle progression. Our data indicates that USP37 expression correlates with transformation by preventing degradation of different oncoproteins. It was found that in osteosarcoma cell lines USP37 is elevated which gives survival advantage to these cells while its depletion leads to enhanced cell death in response to genotoxic stress. USP37 depletion results in reduced resolution of DNA damage foci like gamma H2AX and 53BP1 and increase in no of collapsed replication fork which indicate the reduced ability of cells to carry out constitutive DNA replication. Physically USP37 interacted with proteins involved in DNA damage repair and effected their stability. We tried to correlate our data with archived patient osteosarcoma samples by analyzing if USP37 levels corelate with patient prognosis at our center which will be further discussed. The current data adds a new dimension to this newly explored deubiquitinates and merits development of targeting strategies to explore its therapeutic potential in osteosarcoma. Citation Format: Mayank Singh, Atul Batra, Sameer Bakhshi, Matthew Summers. Validation of Ubiquitin specific peptidases 37 as a prognostic and diagnostic marker in osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1256.