Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1.
Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1.
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DOI：
10.1126/science.1206923
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发表时间：
2011-08-26
期刊：
影响因子：
--
通讯作者：
Myers JN
中科院分区：
文献类型：
--
作者：
Agrawal N;Frederick MJ;Pickering CR;Bettegowda C;Chang K;Li RJ;Fakhry C;Xie TX;Zhang J;Wang J;Zhang N;El-Naggar AK;Jasser SA;Weinstein JN;Treviño L;Drummond JA;Muzny DM;Wu Y;Wood LD;Hruban RH;Westra WH;Koch WM;Califano JA;Gibbs RA;Sidransky D;Vogelstein B;Velculescu VE;Papadopoulos N;Wheeler DA;Kinzler KW;Myers JN
头颈部鳞状细胞癌(HNSCC)是全球第六大常见癌症。为了探索这种癌症的遗传起源，我们使用了全外显子组测序和基因拷贝数分析来研究32个原发肿瘤。有吸烟史患者的肿瘤比不吸烟患者的肿瘤有更多的突变，而人乳头瘤病毒(HPV)阴性的肿瘤比HPV阳性的肿瘤有更多的突变。在多个肿瘤中突变的六个基因在多达88个额外的HNSCC中进行了评估。除了先前描述的TP53、CDKN2A、PIK3CA和HRAS突变外，我们还发现了FBXW7和NOTCH1的突变。有趣的是，在NOTCH1发现的28个突变中，有近40%被预测会截断基因产物，这表明在这种肿瘤类型中，NOTCH1可能是一个肿瘤抑制基因，而不是癌基因。
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To explore the genetic origins of this cancer, we used whole exome sequencing and gene copy number analyses to study 32 primary tumors. Tumors from patients with a history of tobacco use had more mutations than did tumors from patients who did not use tobacco, and tumors that were negative for human papilloma virus (HPV) had more mutations than did HPV-positive tumors. Six of the genes that were mutated in multiple tumors were assessed in up to 88 additional HNSCCs. In addition to previously described mutations in TP53, CDKN2A, PIK3CA and HRAS, we identified mutations in FBXW7 and NOTCH1. Interestingly, nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.
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影响因子：
64.8
作者：
Varela, Ignacio;Tarpey, Patrick;Raine, Keiran;Huang, Dachuan;Ong, Choon Kiat;Stephens, Philip;Davies, Helen;Jones, David;Lin, Meng-Lay;Teague, Jon;Bignell, Graham;Butler, Adam;Cho, Juok;Dalgliesh, Gillian L.;Galappaththige, Danushka;Greenman, Chris;Hardy, Claire;Jia, Mingming;Latimer, Calli;Lau, King Wai;Marshall, John;McLaren, Stuart;Menzies, Andrew;Mudie, Laura;Stebbings, Lucy;Largaespada, David A.;Wessels, L. F. A.;Richard, Stephane;Kahnoski, Richard J.;Anema, John;Tuveson, David A.;Perez-Mancera, Pedro A.;Mustonen, Ville;Fischer, Andrej;Adams, David J.;Rust, Alistair;Chan-on, Waraporn;Subimerb, Chutima;Dykema, Karl;Furge, Kyle;Campbell, Peter J.;Teh, Bin Tean;Stratton, Michael R.;Futreal, P. Andrew
通讯作者：
Futreal, P. Andrew
影响因子：
12.4
作者：
Cohen, LY;Bourbonnière, M;Sékaly, RP
通讯作者：
Sékaly, RP
影响因子：
6.4
作者：
Hafkamp, HC;Speel, EJM;Manni, JJ
通讯作者：
Manni, JJ
胰腺神经内分泌肿瘤中经常改变DAXX/ATRX，MEN1和MTOR途径基因。
DOI：
10.1126/science.1200609
发表时间：
2011-03-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jiao Y;Shi C;Edil BH;de Wilde RF;Klimstra DS;Maitra A;Schulick RD;Tang LH;Wolfgang CL;Choti MA;Velculescu VE;Diaz LA Jr;Vogelstein B;Kinzler KW;Hruban RH;Papadopoulos N
通讯作者：
Papadopoulos N
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P