Development of uveal melanoma xenografts: From patient tumors to patient derived xenografts characterization

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Abstract

50% of uveal melanoma patients die from their metastatic disease showing the necessity to develop efficient therapeutic agents and useful and relevant tool for their preclinical assessment. Thus, we have established and characterized an in vivo panel of xenografts directly obtained from patient uveal melanoma tumors. 90 Samples obtained from patient primary tumors or metastases were subcutaneously grafted into SCID mice. 25 patient derived xenografts (PDX) were obtained and 16 have been characterized. UM histology of the PDX was confirmed by pathological analyses. NA17, Tyrosinase, and Melan-A antigen expressions were positive in all samples. Bcl-2 protein was overexpressed in almost all PDX. GNAQ, GNA11 and BAP1 mutations were observed in 4, 10 and 7 of 15 xenografts. The comparison of genomic alterations showed the same DNA damages as the corresponding patients and the differential genes expression observed was mainly due to difference of stroma between patient tumor and PDX. In vivo therapeutic assessments were being performed and will be presented. Our panel of PDX presents the characteristics similar to the patient’s originated tumors and could constitute a useful preclinical tool for testing new agents and protocols.

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