Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes.
Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes.
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DOI：
10.1038/sj.onc.1210529
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发表时间：
2007-11-01
期刊：
影响因子：
8
通讯作者：
Goodfellow, P. J.
中科院分区：
文献类型：
--
作者：
Pollock, P. M.;Gartside, M. G.;Dejeza, L. C.;Powell, M. A.;Mallon, M. A.;Davies, H.;Mohammadi, M.;Futreal, P. A.;Stratton, M. R.;Trent, J. M.;Goodfellow, P. J.
子宫内膜癌是美国最常见的妇科恶性肿瘤。 /10（30％）子宫内膜细胞系和19/187（10％）原发性子宫肿瘤。亚型（研究18/115例），大多数鉴定出的体细胞突变与FGFR2和FGFR3中的生殖线相同，引起APERT综合征，熊 - 斯坦旺森综合征，下降体性综合症，adchondroplasia，adonondroploploplasia and actdan综合征。鉴定出S252W（在八个肿瘤中）和N550K（在五个样本中）。也可能导致受体功能获得的广泛功能分析，这表明它们通过多种机制导致受体激活。在患有晚期或复发性内膜癌患者中采用抗FGFR分子靶向疗法。
Endometrial carcinoma is the most common gynecological malignancy in the United States. Although most women present with early disease confined to the uterus, the majority of persistent or recurrent tumors are refractory to current chemotherapies. We have identified a total of 11 different FGFR2 mutations in 3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors. Mutations were seen primarily in tumors of the endometrioid histologic subtype (18/115 cases investigated, 16%). The majority of the somatic mutations identified were identical to germline activating mutations in FGFR2 and FGFR3 that cause Apert Syndrome, Beare–Stevenson Syndrome, hypochondroplasia, achondroplasia and SADDAN syndrome. The two most common somatic mutations identified were S252W (in eight tumors) and N550K (in five samples). Four novel mutations were identified, three of which are also likely to result in receptor gain-of-function. Extensive functional analyses have already been performed on many of these mutations, demonstrating they result in receptor activation through a variety of mechanisms. The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma.
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影响因子：
3.5
作者：
Ibrahimi, OA;Zhang, FM;Mohammadi, M
通讯作者：
Mohammadi, M
影响因子：
4
作者：
Möller, B;Rasmussen, C;Olovsson, M
通讯作者：
Olovsson, M
人类癌基因组中体细胞突变的模式。
影响因子：
64.8
作者：
Greenman, Christopher;Stephens, Philip;Smith, Raffaella;Dalgliesh, Gillian L.;Hunter, Christopher;Bignell, Graham;Davies, Helen;Teague, Jon;Butler, Adam;Edkins, Sarah;O'Meara, Sarah;Vastrik, Imre;Schmidt, Esther E.;Avis, Tim;Barthorpe, Syd;Bhamra, Gurpreet;Buck, Gemma;Choudhury, Bhudipa;Clements, Jody;Cole, Jennifer;Dicks, Ed;Forbes, Simon;Gray, Kris;Halliday, Kelly;Harrison, Rachel;Hills, Katy;Hinton, Jon;Jenkinson, Andy;Jones, David;Menzies, Andy;Mironenko, Tatiana;Perry, Janet;Raine, Keiran;Richardson, Dave;Shepherd, Rebecca;Small, Alexandra;Tofts, Calli;Varian, Jennifer;Webb, Tony;West, Sofie;Widaa, Sara;Yates, Andy;Cahill, Daniel P.;Louis, David N.;Goldstraw, Peter;Nicholson, Andrew G.;Brasseur, Francis;Looijenga, Leendert;Weber, Barbara L.;Chiew, Yoke-Eng;deFazio, Anna;Greaves, Mel F.;Green, Anthony R.;Campbell, Peter;Birney, Ewan;Easton, Douglas F.;Chenevix-Trench, Georgia;Tan, Min-Han;Khoo, Sok Kean;Teh, Bin Tean;Yuen, Siu Tsan;Leung, Suet Yi;Wooster, Richard;Futreal, P. Andrew;Stratton, Michael R.
通讯作者：
Stratton, Michael R.
影响因子：
4.4
作者：
Chong, A;Zhang, GL;Bajic, VB
通讯作者：
Bajic, VB
影响因子：
5.3
作者：
Monsonego-Ornan, E;Adar, R;Yayon, A
通讯作者：
Yayon, A