Whole-genome analysis informs breast cancer response to aromatase inhibition.
Whole-genome analysis informs breast cancer response to aromatase inhibition.
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DOI：
10.1038/nature11143
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发表时间：
2012-06-10
期刊：
影响因子：
64.8
通讯作者：
Mardis, Elaine R.
中科院分区：
文献类型：
--
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.
为了将雌激素受体阳性（ER+）乳腺癌的可变临床特征与体细胞改变相关联，我们通过大规模平行测序和分析研究了新辅助芳香化酶抑制剂（AI）治疗研究中患者的治疗前肿瘤活检。鉴定出18个显著突变的基因，包括5个先前与造血系统疾病相关的基因（RUNX1、CBFB、MYH9、MLL3和SF3B1）。突变型MAP3K1与管腔A状态、低级别组织学和低增殖率相关，而突变型TP53与相反的模式相关。此外，突变体GATA 3与AI处理后增殖抑制相关。通路分析表明，MAP3K1底物MAP2K4的突变产生了与MAP3K1缺失相似的扰动。ER+乳腺癌的不同表型与特定的体细胞突变模式相关，这些突变映射到与肿瘤生物学相关的细胞途径中，但大多数复发性突变相对罕见。基于这些发现的前瞻性临床试验将需要全面的基因组测序。
To correlate the variable clinical features of estrogen receptor positive (ER+) breast cancer with somatic alterations, we studied pre-treatment tumour biopsies accrued from patients in a study of neoadjuvant aromatase inhibitor (AI) therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to hematopoietic disorders. Mutant MAP3K1 was associated with Luminal A status, low grade histology and low proliferation rates whereas mutant TP53 associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon AI treatment. Pathway analysis demonstrated mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in ER+ breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumor biology but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
DOI：
10.1016/j.jamcollsurg.2009.01.035
发表时间：
2009-05
影响因子：
5.2
作者：
Olson, John A., Jr.;Budd, G. Thomas;Carey, Lisa A.;Harris, Lyndsay A.;Esserman, Laura J.;Fleming, Gini F.;Marcom, Paul K.;Leight, George S., Jr.;Giuntoli, Therese;Commean, Paul;Bae, Kyongtae;Luo, Jingqin;Ellis, Matthew J.
通讯作者：
Ellis, Matthew J.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1093/jnci/djn309
发表时间：
2008-10-01
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Ellis MJ;Tao Y;Luo J;A'Hern R;Evans DB;Bhatnagar AS;Chaudri Ross HA;von Kameke A;Miller WR;Smith I;Eiermann W;Dowsett M
通讯作者：
Dowsett M
影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R