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 language | English (US) |
|---|---|
| Pages (from-to) | 820-824 |
| Number of pages | 5 |
| Journal | JNCCN Journal of the National Comprehensive Cancer Network |
| Volume | 14 |
| Issue number | 7 |
| State | Published - Jul 1 2016 |
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ASJC Scopus subject areas
- Oncology
Cite this
Whole-exome sequencing in two extreme phenotypes of response to VEGF-targeted therapies in patients with metastatic clear cell renal cell carcinoma. / Fay, Andre P.; De Velasco, Guillermo; Ho, Thai H; Van Allen, Eliezer M.; Murray, Bradley; Albiges, Laurence; Signoretti, Sabina; Hakimi, A. Ari; Stanton, Melissa L.; Bellmunt, Joaquim; McDermott, David F.; Atkins, Michael B.; Garraway, Levi A.; Kwiatkowski, David J.; Choueiri, Toni K.
In: JNCCN Journal of the National Comprehensive Cancer Network, Vol. 14, No. 7, 01.07.2016, p. 820-824.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Whole-exome sequencing in two extreme phenotypes of response to VEGF-targeted therapies in patients with metastatic clear cell renal cell carcinoma
AU - Fay, Andre P.
AU - De Velasco, Guillermo
AU - Ho, Thai H
AU - Van Allen, Eliezer M.
AU - Murray, Bradley
AU - Albiges, Laurence
AU - Signoretti, Sabina
AU - Hakimi, A. Ari
AU - Stanton, Melissa L.
AU - Bellmunt, Joaquim
AU - McDermott, David F.
AU - Atkins, Michael B.
AU - Garraway, Levi A.
AU - Kwiatkowski, David J.
AU - Choueiri, Toni K.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84978910659&partnerID=8YFLogxK
M3 - Article
C2 - 27407122
AN - SCOPUS:84978910659
VL - 14
SP - 820
EP - 824
JO - JNCCN Journal of the National Comprehensive Cancer Network
JF - JNCCN Journal of the National Comprehensive Cancer Network
SN - 1540-1405
IS - 7
ER -