Recurrent PTPRB and PLCG1 mutations in angiosarcoma.
Recurrent PTPRB and PLCG1 mutations in angiosarcoma.
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DOI：
10.1038/ng.2921
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发表时间：
2014-04
期刊：
影响因子：
30.8
通讯作者：
Campbell, Peter J.
中科院分区：
文献类型：
--
作者：
Behjati, Sam;Tarpey, Patrick S.;Sheldon, Helen;Martincorena, Inigo;Van Loo, Peter;Gundem, Gunes;Wedge, David C.;Ramakrishna, Manasa;Cooke, Susanna L.;Pillay, Nischalan;Vollan, Hans Kristian M.;Papaemmanuil, Elli;Koss, Hans;Bunney, Tom D.;Hardy, Claire;Joseph, Olivia R.;Martin, Sancha;Mudie, Laura;Butler, Adam;Teague, Jon W.;Patil, Meena;Steers, Graham;Cao, Yu;Gumbs, Curtis;Ingram, Davis;Lazar, Alexander J.;Little, Latasha;Mahadeshwar, Harshad;Protopopov, Alexei;Al Sannaa, Ghadah A.;Seth, Sahil;Song, Xingzhi;Tang, Jiabin;Zhang, Jianhua;Ravi, Vinod;Torres, Keila E.;Khatri, Bhavisha;Halai, Dina;Roxanis, Ioannis;Baumhoer, Daniel;Tirabosco, Roberto;Amary, M. Fernanda;Boshoff, Chris;McDermott, Ultan;Katan, Matilda;Stratton, Michael R.;Futreal, P. Andrew;Flanagan, Adrienne M.;Harris, Adrian;Campbell, Peter J.
血管肉瘤是一种侵袭性的恶性肿瘤，可自发或继发于电离辐射或慢性淋巴水肿。以前的工作已经确定异常血管生成，包括血管生成信号基因的偶尔体细胞突变，作为血管肉瘤的关键驱动因素。在此，我们采用全基因组、外显子组和靶向测序来研究原发性和继发性血管肉瘤的体细胞变化。我们确定了两个基因，PTPRB和PLCG 1，这是密切相关的血管生成的复发性突变。内皮磷酸酶PTPRB是血管生长因子酪氨酸激酶的负调节因子，在10/39（26%）的肿瘤中主要存在截短突变。PLCG 1是酪氨酸激酶的信号转导子，在3/34例（9%）病例中表现为复发性的、可能激活的R707 Q错义变体。总体而言，15/39（38%）的肿瘤在血管生成信号基因中携带至少一个驱动突变。我们的研究结果为目前针对血管肉瘤血管生成信号的治疗提供了信息，并加强了这种治疗。
Angiosarcoma is an aggressive malignancy that arises spontaneously or secondarily to ionising radiation or chronic lymphoedema. Previous work has identified aberrant angiogenesis, including occasional somatic mutations in angiogenesis signalling genes, as a key driver of angiosarcoma. Here, we employed whole genome, exome, and targeted sequencing to study the somatic changes underpinning primary and secondary angiosarcoma. We identified recurrent mutations in two genes, PTPRB and PLCG1, which are intimately linked to angiogenesis. The endothelial phosphatase PTPRB, a negative regulator of vascular growth factor tyrosine kinases, harboured predominantly truncating mutations in 10/39 (26%) tumours. PLCG1, a signal transducer of tyrosine kinases, presented with a recurrent, likely activating R707Q missense variant in 3/34 cases (9%). Overall, 15/39 (38%) tumours harboured at least one driver mutation in angiogenesis signalling genes. Our findings inform and reinforce current therapeutic efforts to target angiogenesis signalling in angiosarcoma.
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影响因子：
3.7
作者：
Guo, Tianhua;Zhang, Lei;Chang, Ning-En;Singer, Samuel;Maki, Robert G.;Antonescu, Cristina R.
通讯作者：
Antonescu, Cristina R.
影响因子：
46.9
作者：
Trapnell C;Williams BA;Pertea G;Mortazavi A;Kwan G;van Baren MJ;Salzberg SL;Wold BJ;Pachter L
通讯作者：
Pachter L
宇宙（癌症中的体细胞突变目录）数据库和网站。
影响因子：
8.8
作者：
Bamford, S;Dawson, E;Forbes, S;Clements, J;Pettett, R;Dogan, A;Flanagan, A;Teague, J;Futreal, PA;Stratton, MR;Wooster, R
通讯作者：
Wooster, R
DOI：
10.1056/nejmoa1102140
发表时间：
2012-01-26
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ombrello MJ;Remmers EF;Sun G;Freeman AF;Datta S;Torabi-Parizi P;Subramanian N;Bunney TD;Baxendale RW;Martins MS;Romberg N;Komarow H;Aksentijevich I;Kim HS;Ho J;Cruse G;Jung MY;Gilfillan AM;Metcalfe DD;Nelson C;O'Brien M;Wisch L;Stone K;Douek DC;Gandhi C;Wanderer AA;Lee H;Nelson SF;Shianna KV;Cirulli ET;Goldstein DB;Long EO;Moir S;Meffre E;Holland SM;Kastner DL;Katan M;Hoffman HM;Milner JD
通讯作者：
Milner JD
影响因子：
4.8
作者：
Everett, Katy L.;Bunney, Tom D.;Katan, Matilda
通讯作者：
Katan, Matilda