Whole-Exome Sequencing in Two Extreme Phenotypes of Response to VEGF-Targeted Therapies in Patients With Metastatic Clear Cell Renal Cell Carcinoma

被引：36

作者：

Fay, Andre P. ^{[1
]}

de Velasco, Guillermo ^{[1
]}

Ho, Thai H. ^{[2
]}

Van Allen, Eliezer M. ^{[1
,3
]}

Murray, Bradley ^{[3
]}

Albiges, Laurence ^{[1
]}

Signoretti, Sabina ^{[4
]}

Hakimi, A. Ari ^{[5
]}

Stanton, Melissa L. ^{[6
]}

Bellmunt, Joaquim ^{[1
]}

McDermott, David F. ^{[7
]}

Atkins, Michael B. ^{[7
,8
]}

Garraway, Levi A. ^{[1
,3
]}

Kwiatkowski, David J. ^{[9
]}

Choueiri, Toni K. ^{[1
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Mayo Clin, Div Hematol & Oncol, Scottsdale, AZ USA

[3] MIT & Harvard, Broad Inst, Cambridge, MA USA

[4] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[5] Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA

[6] Mayo Clin, Dept Lab Med Pathol, Scottsdale, AZ USA

[7] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA

[8] Georgetown Lombardi Comprehens Canc Ctr, Dept Med Oncol, Washington, DC USA

[9] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

来源：

JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK | 2016年 / 14卷 / 07期

关键词：

IMPACT; PBRM1;

D O I：

10.6004/jnccn.2016.0086

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：820 / +

页数：8

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