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

Andre P. Fay, Guillermo De Velasco, Thai H. Ho, Eliezer M. Van Allen, Bradley Murray, Laurence Albiges, Sabina Signoretti, A. Ari Hakimi, Melissa L. Stanton, Joaquim Bellmunt, David F. McDermott, Michael B. Atkins, Levi A. Garraway, David J. Kwiatkowski, Toni K. Choueiri

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)820-824
Number of pages5
JournalJNCCN Journal of the National Comprehensive Cancer Network
Volume14
Issue number7
DOIs
StatePublished - Jul 1 2016

ASJC Scopus subject areas

  • Oncology

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    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. (2016). Whole-exome sequencing in two extreme phenotypes of response to VEGF-targeted therapies in patients with metastatic clear cell renal cell carcinoma. JNCCN Journal of the National Comprehensive Cancer Network, 14(7), 820-824. https://doi.org/10.6004/jnccn.2016.0086