Genome sequencing identifies a basis for everolimus sensitivity.
Genome sequencing identifies a basis for everolimus sensitivity.
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DOI：
10.1126/science.1226344
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发表时间：
2012-10-12
期刊：
影响因子：
--
通讯作者：
Solit DB
中科院分区：
文献类型：
--
作者：
Iyer G;Hanrahan AJ;Milowsky MI;Al-Ahmadie H;Scott SN;Janakiraman M;Pirun M;Sander C;Socci ND;Ostrovnaya I;Viale A;Heguy A;Peng L;Chan TA;Bochner B;Bajorin DF;Berger MF;Taylor BS;Solit DB
抗癌药物通常会在一小部分患者中引起戏剧性反应。我们使用全基因组测序研究了一名接受伊波利莫斯治疗的转移性膀胱癌患者持久缓解的遗传学基础，伊波利莫斯是一种抑制mTOR(雷帕霉素的哺乳动物靶点)信号通路的药物。在这些体细胞突变中，有一个是TSC1(结节性硬化症复合体1)的功能丧失突变，TSC1是mTOR途径激活的调节因子。靶向测序显示，在另外109例接受检查的膀胱癌中，约有8%的人发生了TSC1突变，而TSC1突变与依维莫司的敏感性有关。这些结果证明了在临床环境中使用全基因组测序来识别以前神秘的药物敏感性生物标记物的可行性，这些生物标记物可以帮助识别最有可能对靶向抗癌药物有反应的患者。
Cancer drugs often induce dramatic responses in a small minority of patients. We used whole-genome sequencing to investigate the genetic basis of a durable remission of metastatic bladder cancer in a patient treated with everolimus, a drug that inhibits the mTOR (mammalian target of rapamycin) signaling pathway. Among the somatic mutations was a loss-of-function mutation in TSC1 (tuberous sclerosis complex 1), a regulator of mTOR pathway activation. Targeted sequencing revealed TSC1 mutations in about 8% of 109 additional bladder cancers examined, and TSC1 mutation correlated with everolimus sensitivity. These results demonstrate the feasibility of using whole-genome sequencing in the clinical setting to identify previously occult biomarkers of drug sensitivity that can aid in the identification of patients most likely to respond to targeted anticancer drugs.
影响因子：
158.5
作者：
Krueger, Darcy A.;Care, Marguerite M.;Franz, David Neal
通讯作者：
Franz, David Neal
影响因子：
11.5
作者：
Platt, Fiona M.;Hurst, Carolyn D.;Knowles, Margaret A.
通讯作者：
Knowles, Margaret A.
影响因子：
5.3
作者：
Lopez-Lago, Miguel A.;Okada, Tomoyo;Giancotti, Filippo G.
通讯作者：
Giancotti, Filippo G.