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Table S2 from Mutations in TSC1, TSC2, and MTOR Are Associated with Response to Rapalogs in Patients with Metastatic Renal Cell Carcinoma
journal contribution
posted on 2023-03-31, 18:45 authored by David J. Kwiatkowski, Toni K. Choueiri, André P. Fay, Brian I. Rini, Aaron R. Thorner, Guillermo de Velasco, Magdalena E. Tyburczy, Lana Hamieh, Laurence Albiges, Neeraj Agarwal, Thai H. Ho, Jiaxi Song, Jean-Christophe Pignon, Pablo M. Barrios, M. Dror Michaelson, Eliezer M. Van Allen, Katherine M. Krajewski, Camillo Porta, Sumanta Kumar Pal, Joaquim Bellmunt, David F. McDermott, Daniel Y.C. Heng, Kathryn P. Gray, Sabina SignorettiList of all patients with complete information on mutations found and allele frequency
Funding
NIH/NCI DF/HCC and Kidney Cancer
NIH/NCI
Michael Brigham Funds, for Kidney Cancer Research
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ARTICLE ABSTRACT
Purpose: We examined the hypothesis that mutations in mTOR pathway genes are associated with response to rapalogs in metastatic renal cell carcinoma (mRCC).Experimental Design: We studied a cohort of mRCC patients who were treated with mTOR inhibitors with distinct clinical outcomes. Tumor DNA from 79 subjects was successfully analyzed for mutations using targeted next-generation sequencing of 560 cancer genes. Responders were defined as those with partial response (PR) by RECIST v1.0 or stable disease with any tumor shrinkage for 6 months or longer. Nonresponders were defined as those with disease progression during the first 3 months of therapy. Fisher exact test assessed the association between mutation status in mTOR pathway genes and treatment response.Results: Mutations in MTOR, TSC1, or TSC2 were more common in responders, 12 (28%) of 43, than nonresponders, 4 (11%) of 36 (P = 0.06). Mutations in TSC1 or TSC2 alone were also more common in responders, 9 (21%), than nonresponders, 2(6%), (P = 0.05). Furthermore, 5 (42%) of 12 subjects with PR had mutations in MTOR, TSC1, or TSC2 compared with 4 (11%) of 36 nonresponders (P = 0.03). Eight additional non-mTOR pathway genes were found to be mutated in at least 4 of 79 tumors (5%); none were associated positively with response.Conclusions: In this cohort of mRCC patients, mutations in MTOR, TSC1, or TSC2 were more common in patients who experienced clinical benefit from rapalogs than in those who progressed. However, a substantial fraction of responders (24 of 43, 56%) had no mTOR pathway mutation identified. Clin Cancer Res; 22(10); 2445–52. ©2016 AACR.See related commentary by Voss and Hsieh, p. 2320Usage metrics
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