Work

Pd46-07 Genotype-phenotype Associations in Von Hippel-lindau

Year: 2018

Type: article

Abstract: RESULTS: Sorafenib/Sunitinib monotherapy, combined or alternating treatment groups demonstrated more significant anti-tumor activity, as compared to Axitinib monotherapy (P<0.05).Most interestingly, the PDX of KI2368, in contrast to KI2367, demonstrated significant 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 influence the clinical outcome of targeted therapies.Multiple biopsy and genomic analysis of intra-tumor molecular heterogeneity could potentially help guide more effective plan in selecting targeted therapies for ccRCC patients.

Source: The Journal of Urology

DOI: 10.1016/j.juro.2018.02.2155