Whole-exome sequencing in two extreme phenotypes of response to VEGF-targeted therapies in patients with metastatic clear cell renal cell carcinoma Journal Article


Authors: Fay, A. P.; de Velasco, G.; Ho, T. H.; Van Allen, E. M.; Murray, B.; Albiges, L.; Signoretti, S.; Hakimi, A. A.; Stanton, M. L.; Bellmunt, J.; McDermott, D. F.; Atkins, M. B.; Garraway, L. A.; Kwiatkowski, D. J.; Choueiri, T. K.
Article Title: Whole-exome sequencing in two extreme phenotypes of response to VEGF-targeted therapies in patients with metastatic clear cell renal cell carcinoma
Abstract: Advances in next-generation sequencing have provided a unique opportunity to understand the biology of disease and mechanisms of sensitivity or resistance to specific agents. Renal cell carcinoma (RCC) is a heterogeneous disease and highly variable clinical responses have been observed with vascular endothelial growth factor (VEGF)-targeted therapy (VEGF-TT). We hypothesized that whole-exome sequencing analysis might identify genotypes associated with extreme response or resistance to VEGF-TT in metastatic (mRCC). Patients with mRCC who had received first-line sunitinib or pazopanib and were in 2 extreme phenotypes of response were identified. Extreme responders (ERs) were defined as those with partial response or complete response for 3 or more years (n=13) and primary refractory patients (PRPs) were defined as those with progressive disease within the first 3 months of therapy (n=14). International Metastatic RCC Database Consortium prognostic scores were not significantly different between the groups (P=.67). Considering the genes known to be mutated in RCC at significant frequency, PBRM1 mutations were identified in 7 ERs (54%) versus 1 PRP (7%) (P=.01). In addition, mutations in TP53 (n=4) were found only in PRPs (P=.09). Our data suggest that mutations in some genes in RCC may impact response to VEGF-TT. © JNCCN - Journal of the National Comprehensive Cancer Network.
Journal Title: Journal of the National Comprehensive Cancer Network
Volume: 14
Issue: 7
ISSN: 1540-1405
Publisher: Harborside Press  
Date Published: 2016-07-01
Start Page: 820
End Page: 824
Language: English
PROVIDER: scopus
PUBMED: 27407122
PMCID: PMC5582541
DOI/URL:
Notes: Article -- Export Date: 2 August 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Abraham Ari Hakimi
    324 Hakimi