A refined molecular taxonomy of breast cancer.
A refined molecular taxonomy of breast cancer.
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DOI：
10.1038/onc.2011.301
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发表时间：
2012-03-01
期刊：
影响因子：
8
通讯作者：
Theillet, C.
中科院分区：
文献类型：
--
作者：
Guedj, M.;Marisa, L.;de Reynies, A.;Orsetti, B.;Schiappa, R.;Bibeau, F.;MacGrogan, G.;Lerebours, F.;Finetti, P.;Longy, M.;Bertheau, P.;Bertrand, F.;Bonnet, F.;Martin, A. L.;Feugeas, J. P.;Bieche, I.;Lehmann-Che, J.;Lidereau, R.;Birnbaum, D.;Bertucci, F.;de The, H.;Theillet, C.
目前的组织临床乳腺癌分类简单但不精确。已经提出了几种基于表达谱的乳腺癌分子分类作为替代方案。然而，它们的可靠性和临床实用性一再受到质疑，特别是因为它们大多数来自相对较小的初始患者群体。我们使用三种无监督分类方法分析了 537 个乳腺肿瘤的转录组。通过所有三种方法将 355 个肿瘤的核心子集分配到六个簇。这六个亚组与先前定义的乳腺癌分子类别重叠，但也显示出重要的差异，特别是缺乏 ERBB2 亚组以及将大管腔 ER+ 组分为四个亚组，其中两个亚组具有高度增殖性。在六个亚组中，四个为 ER+/PR+/AR+，一个为 ER−/PR−/AR+，一个为三阴性 (AR−/ER−/PR−)。 ERBB2 扩增的肿瘤分为 ER−/PR−/AR+ 亚组和高度增殖的 ER+ LumC 亚组。重要的是，这六个分子亚组中的每一个都显示出特定的拷贝数改变。基因表达变化与特定信号通路相关。这六个亚组中的每一个在肿瘤分级、转移部位、无复发生存或化疗反应方面都表现出非常显着的差异。所有这些发现均在包括 3000 多个肿瘤的大型外部数据集上得到验证。因此，我们的数据表明这六个分子亚组代表了明确的乳腺癌临床生物学实体。它们的鉴定应有助于检测乳腺癌的新预后因素或治疗靶点。
The current histoclinical breast cancer classification is simple but imprecise. Several molecular classifications of breast cancers based on expression profiling have been proposed as alternatives. However, their reliability and clinical utility have been repeatedly questioned, notably because most of them were derived from relatively small initial patient populations. We analyzed the transcriptomes of 537 breast tumors using three unsupervised classification methods. A core subset of 355 tumors was assigned to six clusters by all three methods. These six subgroups overlapped with previously defined molecular classes of breast cancer, but also showed important differences, notably the absence of an ERBB2 subgroup and the division of the large luminal ER+ group into four subgroups, two of them being highly proliferative. Of the six subgroups, four were ER+/PR+/AR+, one was ER−/PR−/AR+ and one was triple negative (AR−/ER−/PR−). ERBB2-amplified tumors were split between the ER−/PR−/AR+ subgroup and the highly proliferative ER+ LumC subgroup. Importantly, each of these six molecular subgroups showed specific copy-number alterations. Gene expression changes were correlated to specific signaling pathways. Each of these six subgroups showed very significant differences in tumor grade, metastatic sites, relapse-free survival or response to chemotherapy. All these findings were validated on large external datasets including more than 3000 tumors. Our data thus indicate that these six molecular subgroups represent well-defined clinico-biological entities of breast cancer. Their identification should facilitate the detection of novel prognostic factors or therapeutical targets in breast cancer.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Carroll, Jason S.;Meyer, Clifford A.;Brown, Myles
通讯作者：
Brown, Myles
影响因子：
11.2
作者：
Smid, Marcel;Wang, Yixin;Martens, John W. M.
通讯作者：
Martens, John W. M.
影响因子：
8
作者：
Farmer, P;Bonnefoi, H;Iggo, R
通讯作者：
Iggo, R
影响因子：
4.4
作者：
Kapp, Amy V.;Jeffrey, Stefanie S.;Langerod, Anita;Borresen-Dale, Anne-Lise;Han, Wonshik;Noh, Dong-Young;Bukholm, Ida R. K.;Nicolau, Monica;Brown, Patrick O.;Tibshirani, Robert
通讯作者：
Tibshirani, Robert