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DOI | 10.1126/science.aan5951 |
Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma | |
Miao, Diana1,2,3; Margolis, Claire A.1,2,3; Gao, Wenhua1; Voss, Martin H.4,5; Li, Wei6; Martini, Dylan J.1; Norton, Craig1; Bosse, Dominick1; Wankowicz, Stephanie M.1,2,3; Cullen, Dana7; Horak, Christine7; Wind-Rotolo, Megan7; Tracy, Adam2,3; Giannakis, Marios1,2,3; Hodi, Frank Stephen1; Drake, Charles G.8; Ball, Mark W.9,10; Allaf, Mohamad E.9,10; Snyder, Alexandra4,13; Hellmann, Matthew D.4,5; Ho, Thai11; Motzer, Robert J.4,5; Signoretti, Sabina1; Kaelin, William G., Jr.1,12; Choueiri, Toni K.1; Van Allen, Eliezer M.1,2,3 | |
2018-02-16 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 359期号:6377页码:801-805 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Immune checkpoint inhibitors targeting the programmed cell death 1 receptor (PD-1) improve survival in a subset of patients with clear cell renal cell carcinoma (ccRCC). To identify genomic alterations in ccRCC that correlate with response to anti-PD-1 monotherapy, we performed whole-exome sequencing of metastatic ccRCC from 35 patients. We found that clinical benefit was associated with loss-of-function mutations in the PBRM1 gene (P = 0.012), which encodes a subunit of the PBAF switch-sucrose nonfermentable (SWI/SNF) chromatin remodeling complex. We confirmed this finding in an independent validation cohort of 63 ccRCC patients treated with PD-1 or PD-L1 (PD-1 ligand) blockade therapy alone or in combination with anti-CTLA-4 (cytotoxic T lymphocyte-associated protein 4) therapies (P = 0.0071). Gene-expression analysis of PBAF-deficient ccRCC cell lines and PBRM1-deficient tumors revealed altered transcriptional output in JAK-STAT (Janus kinase-signal transducers and activators of transcription), hypoxia, and immune signaling pathways. PBRM1 loss in ccRCC may alter global tumor-cell expression profiles to influence responsiveness to immune checkpoint therapy. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000425116200047 |
WOS关键词 | CTLA-4 BLOCKADE ; PD-1 BLOCKADE ; PBRM1 ; TUMORS ; MUTATIONS ; EXPRESSION ; EVEROLIMUS ; RESISTANCE ; SUNITINIB ; NIVOLUMAB |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/197996 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA; 2.MIT, Broad Inst, Cambridge, MA 02142 USA; 3.Harvard, Cambridge, MA 02142 USA; 4.Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA; 5.Weill Cornell Med Coll, New York, NY 10065 USA; 6.Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA; 7.Bristol Myers Squibb, New York, NY 10154 USA; 8.Columbia Univ, Med Ctr, New York, NY 10032 USA; 9.Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA; 10.Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21287 USA; 11.Mayo Clin, Scottsdale, AZ 85259 USA; 12.Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02215 USA; 13.Adapt Biotechnol, Seattle, WA 98102 USA |
推荐引用方式 GB/T 7714 | Miao, Diana,Margolis, Claire A.,Gao, Wenhua,et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma[J]. SCIENCE,2018,359(6377):801-805. |
APA | Miao, Diana.,Margolis, Claire A..,Gao, Wenhua.,Voss, Martin H..,Li, Wei.,...&Van Allen, Eliezer M..(2018).Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma.SCIENCE,359(6377),801-805. |
MLA | Miao, Diana,et al."Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma".SCIENCE 359.6377(2018):801-805. |
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