RESULTS: Sorafenib/Sunitinib monotherapy, combined or alternating treatment groups demonstrated more significant anti-tumor activity, as compared to Axitinib monotherapy (P<0.05). Most inter- estingly, the PDX of KI2368, in contrast to KI2367, demonstrated sig- nificant anti-tumor activity to Sunitinib monotherapy, Sorafenib and Sunitinib combination and alternating treatment groups, but not to Sorafenib or Axitinib monotherapy (P<0.05). A total of 1725 genes have > 5-fold higher expression levels in KI2367 than in KI2368, including the relevant drug targets: PDGFA, PDGFB and PDGFRA. A total of 994 genes have > 5-fold higher expression in KI2368 than in KI2367. Against human reference genome, 5539 and 5827 protein change variants were respectively found in KI2367 and KI2368, 4023 common variants in both samples. We also found 20 and 4 in-frame gene fusions in KI2367 and KI2368, but no common in-frame fusion was detected. CONCLUSIONS: These results suggest the presence of the intra-tumor molecular heterogeneity in this patient, which could influ- ence the clinical outcome of targeted therapies. Multiple biopsy and genomic analysis of intra-tumor molecular heterogeneity could poten- tially help guide more effective plan in selecting targeted therapies for ccRCC patients. Source of Funding: National Natural Science Foundation of China (Grant No. 81372138) PD46-06 NOVEL INSIGHTS ON WILM’S TUMOR: USING HUMAN NEPHRON PROGENITORS Astgik Petrosyan*, Stefano Da Sacco, Roger E. De Filippo, Laura Perin, Los Angeles, CA INTRODUCTION AND OBJECTIVES: Wilms tumor (WT), a pediatric cancer also known as nephroblastoma, accounts for 95% of renal malignancies in children. Currently little is known of WT formation, and less than half of these tumors are diagnosed at Stage 1 due to their asymptomatic nature. The presence of nephron progenitors (NP) characterized by the expression of CITED1 and/or SIX2 determine the aggressive state of the tumor. However, due to past inability to isolate live human WT CITED1 and/or SIX2 positive cells, little is known about their cell biology and involvement in tumor progression. METHODS: To answer these questions, we used immunoflu- orescence to characterize WT samples and identified CITED1þ, SIX2þ and CITED1SIX2þ cells within WT samples and compared our findings with NP isolated from human fetal renal samples. In addition, using our established Smartflare isolation methods, we obtained live CITED1SIX2 positive cells from WT samples, isolated RNA and performed RNA-Seq. RESULTS: We confirm the expression of CITED1 and SIX2 positive cells within the WT samples, and for the first time we also established the existence of a side population expressing both CITED1 and SIX2, as observed in the true NP within the human fetal kidney at week gestation 16. Further characterization of the WT also identified the absence of mature renal cell markers such as Nephrin and Aquaporin along with the absence of renal developmental markers such as Cal- bindin and LEF1. However, unlike NP from fetal kidney, some WT cells express NPHS2 and WT1 similarly to developing structure such as the renal vesicle, C-shaped bodies, S-shaped bodies, and glomeruli. Using Smartflare technology we have identified on average 6.7% SIX2þ, 0.1% CITED1þ, and 12.43% CITED1SIX2þ cells, while human fetal samples express .16% of CITED1SIX2þ, 19.8% of SIX2þ and hardly any CITED1þ cells. Our RNA-Seq analysis identified different pathways expressed between NP isolated from fetal kidney and WT, specifically in relation to their cell cycle and cell cycle regulators. CONCLUSIONS: This work suggests that we can identify and select for the first time CITED1SIX2 cell present within the WT. RNA- Seq data showed the presence of mechanisms essential for tumor formation. The discovery of this mechanism can help the development of new strategies aimed at halting tumor progression. Source of Funding: None PD46-07 GENOTYPE-PHENOTYPE ASSOCIATIONS IN VON HIPPEL- LINDAU Mark Ball*, Cathy Vocke, Cristiane Leite, James Peterson, Maria Merino, Lindsay Middelton, Prashant Chittiboina, Kareem Zaghloul, Emily Chew, Ashkan Malayeri, Adam Metwalli, Berton Zbar, Laura Schmidt, W. Marston Linehan, Bethesda, MD INTRODUCTION AND OBJECTIVES: von-Hippel Lindau (VHL) disease is an autosomal dominant inherited disorder in which affected individuals develop cystic and solid growth in multiple organs. While VHL is caused by germline alterations of the VHL gene, the manner of allelic loss is variable. Previous work has shown there may be geno- type-phenotype effects in VHL, wherein the manner of alteration of VHL affects the phenotypic manifestations of the disease. We sought to characterize the genotype-phenotype alterations seen in a large cohort of patients treated at our institution. METHODS: A prospective registry of patients with VHL treated at the National Cancer Institute was queried for germline mutation type and phenotypic manifestations. Germline mutations were categorized into missense, partial deletion, nonsense, frameshift, complete deletion, splice site alteration, amino acid insertion/deletion, or silent. The following manifestations were assessed: central nervous system (CNS) hemangioblastomas, retinal angiomas, endolymphatic sac tumor, solid kidney tumors, kidney cysts, pheochromocytoma, solid pancreatic tu- mors, pancreatic cysts, and epididymal cyst adenomas. Patients were excluded if neither their personal nor family genotype were known. RESULTS: A total of 766 patients with genotype and phenotype information representing 402 VHL families were available for analysis. Table 1 demonstrates phenotypic associations by germline mutation type. The most common manifestation was CNS hemangioblastomas, with 78.9% of individuals found to be affected. Solid kidney tumors were seen in 57.3% of patients. Patients with complete deletions were at lower risk for development of several manifestations relative to the rest of the cohort, including solid kidney tumors, retinal angiomas, endo- lymphatic sac tumors and pheochromocytomas. Patients with missense mutations have an increased frequency of pheochromocytomas but reduced occurrence of renal tumors when compared to patients with other mutation types. CONCLUSIONS: These data indicate that there is a genotype- phenotype effect in VHL. These findings have potential implications for screening and may provide insight into disease biology. Vol. 199, No. 4S, Supplement, Sunday, May 20, 2018 THE JOURNAL OF UROLOGY â e893