The prognostic effects of somatic mutations in ER-positive breast cancer.
The prognostic effects of somatic mutations in ER-positive breast cancer.
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DOI：
10.1038/s41467-018-05914-x
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发表时间：
2018-09-04
影响因子：
16.6
通讯作者：
Ellis MJ
中科院分区：
文献类型：
--
作者：
Griffith OL;Spies NC;Anurag M;Griffith M;Luo J;Tu D;Yeo B;Kunisaki J;Miller CA;Krysiak K;Hundal J;Ainscough BJ;Skidmore ZL;Campbell K;Kumar R;Fronick C;Cook L;Snider JE;Davies S;Kavuri SM;Chang EC;Magrini V;Larson DE;Fulton RS;Liu S;Leung S;Voduc D;Bose R;Dowsett M;Wilson RK;Nielsen TO;Mardis ER;Ellis MJ
在此，我们报告使用来自 625 名绝经后（UBC-TAM 系列）和 328 名绝经前（MA12 试验）激素受体阳性 (HR+) 患者的原发性乳腺癌样本的 DNA 对 83 个基因进行靶向测序，以确定体细胞突变与预后之间的相互作用。使用 METABRIC 研究的数据实现了预后相互作用的独立验证。观察到先前建立的 MAP3K1 和 PIK3CA 突变与管腔 A 状态/良好预后以及 TP53 突变与管腔 B/非管腔肿瘤/不良预后之间的关联，验证了该方法。在 UBC-TAM 中，NF1 移码无义 (FS/NS) 突变也是一个不良结果驱动因素，这一点在 METABRIC 中得到了验证。对于 MA12，与 PIK3R1 突变相关的不良结果也是可重复的。尽管进行了严格的错误发现校正，DDR1 突变仍与 UBC-TAM 的不良预后密切相关 (q = 0.0003)。总之，应该进一步探索不常见的复发性体细胞突变，以便对 ER+ 乳腺癌典型的高度可变的结果做出更完整的解释。揭示雌激素阳性（ER+）乳腺癌体细胞突变与预后之间的联系需要使用长期随访数据。在这里，作者结合存档的福尔马林固定石蜡包埋组织和三组 ER+ 乳腺癌队列的靶向测序，发现 NF1 移码无义突变、PIK3R1 突变和 DDR1 突变与临床结果相关。
Here we report targeted sequencing of 83 genes using DNA from primary breast cancer samples from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation and prognosis. Independent validation of prognostic interactions was achieved using data from the METABRIC study. Previously established associations between MAP3K1 and PIK3CA mutations with luminal A status/favorable prognosis and TP53 mutations with Luminal B/non-luminal tumors/poor prognosis were observed, validating the methodological approach. In UBC-TAM, NF1 frame-shift nonsense (FS/NS) mutations were also a poor outcome driver that was validated in METABRIC. For MA12, poor outcome associated with PIK3R1 mutation was also reproducible. DDR1 mutations were strongly associated with poor prognosis in UBC-TAM despite stringent false discovery correction (q = 0.0003). In conclusion, uncommon recurrent somatic mutations should be further explored to create a more complete explanation of the highly variable outcomes that typifies ER+ breast cancer. Unravelling the link between somatic mutation and prognosis in estrogen positive (ER+) breast cancer requires the use of long-term follow-up data. Here, combining archival formalin-fixed paraffin embedded tissue and targeted sequencing in three cohorts of ER+ breast cancer, the authors find associations with clinical outcome for NF1 frame-shift nonsense mutations, PIK3R1 mutation, and DDR1 mutations.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
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：
11.2
作者：
Endesfelder D;Burrell R;Kanu N;McGranahan N;Howell M;Parker PJ;Downward J;Swanton C;Kschischo M
通讯作者：
Kschischo M
影响因子：
28.2
作者：
Haricharan S;Punturi N;Singh P;Holloway KR;Anurag M;Schmelz J;Schmidt C;Lei JT;Suman V;Hunt K;Olson JA Jr;Hoog J;Li S;Huang S;Edwards DP;Kavuri SM;Bainbridge MN;Ma CX;Ellis MJ
通讯作者：
Ellis MJ
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