The molecular diversity of Luminal A breast tumors.
The molecular diversity of Luminal A breast tumors.
复制标题
DOI：
10.1007/s10549-013-2699-3
复制
发表时间：
2013-10
影响因子：
3.8
通讯作者：
Schultz, Nikolaus
中科院分区：
文献类型：
--
作者：
Ciriello, Giovanni;Sinha, Rileen;Hoadley, Katherine A.;Jacobsen, Anders S.;Reva, Boris;Perou, Charles M.;Sander, Chris;Schultz, Nikolaus
乳腺癌是一组具有不同分子特征、预后和治疗选择的疾病。Luminal A型乳腺癌是分子和临床上最异质的。使用来自多项研究的1,000多个Luminal A肿瘤的基因组数据，我们分析了这种肿瘤亚型的拷贝数和突变景观。该综合分析揭示了由不同的拷贝数和突变谱定义的四种主要亚型。我们发现了一种非典型的Luminal A亚型，其特征是高基因组不稳定性、TP 53突变和增加的Aurora激酶信号传导;这些基因组改变导致更差的临床预后。染色体1、8和16的畸变以及PIK 3CA、GATA 3、AKT 1和MAP 3 K1突变驱动其他亚型。最后，无偏途径分析揭示了多个罕见的，但相互排斥的，与辅阻遏物复合物N-Cor和SMRT的活性丧失相关的改变。这些罕见的改变在管腔A肿瘤中最普遍，并可能预测对内分泌治疗的抵抗。我们的工作提供了进一步的分子分层的Luminal A乳腺肿瘤，具有潜在的直接临床意义。本文的在线版本（doi：10.1007/s10549-013-2699-3）包含补充材料，可供授权用户使用。
Breast cancer is a collection of diseases with distinct molecular traits, prognosis, and therapeutic options. Luminal A breast cancer is the most heterogeneous, both molecularly and clinically. Using genomic data from over 1,000 Luminal A tumors from multiple studies, we analyzed the copy number and mutational landscape of this tumor subtype. This integrated analysis revealed four major subtypes defined by distinct copy-number and mutation profiles. We identified an atypical Luminal A subtype characterized by high genomic instability, TP53 mutations, and increased Aurora kinase signaling; these genomic alterations lead to a worse clinical prognosis. Aberrations of chromosomes 1, 8, and 16, together with PIK3CA, GATA3, AKT1, and MAP3K1 mutations drive the other subtypes. Finally, an unbiased pathway analysis revealed multiple rare, but mutually exclusive, alterations linked to loss of activity of co-repressor complexes N-Cor and SMRT. These rare alterations were the most prevalent in Luminal A tumors and may predict resistance to endocrine therapy. Our work provides for a further molecular stratification of Luminal A breast tumors, with potential direct clinical implications. The online version of this article (doi:10.1007/s10549-013-2699-3) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
64.5
作者：
Nik-Zainal S;Van Loo P;Wedge DC;Alexandrov LB;Greenman CD;Lau KW;Raine K;Jones D;Marshall J;Ramakrishna M;Shlien A;Cooke SL;Hinton J;Menzies A;Stebbings LA;Leroy C;Jia M;Rance R;Mudie LJ;Gamble SJ;Stephens PJ;McLaren S;Tarpey PS;Papaemmanuil E;Davies HR;Varela I;McBride DJ;Bignell GR;Leung K;Butler AP;Teague JW;Martin S;Jönsson G;Mariani O;Boyault S;Miron P;Fatima A;Langerød A;Aparicio SA;Tutt A;Sieuwerts AM;Borg Å;Thomas G;Salomon AV;Richardson AL;Børresen-Dale AL;Futreal PA;Stratton MR;Campbell PJ;Breast Cancer Working Group of the International Cancer Genome Consortium
通讯作者：
Breast Cancer Working Group of the International Cancer Genome Consortium