How different are luminal A and basal breast cancers?
How different are luminal A and basal breast cancers?
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DOI：
10.1002/ijc.24055
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发表时间：
2009-03-15
影响因子：
6.4
通讯作者：
Birnbaum, Daniel
中科院分区：
文献类型：
--
作者：
Bertucci, Francois;Finetti, Pascal;Birnbaum, Daniel
乳腺癌的异质性使其演变难以预测，其治疗也远未达到最佳水平。至少存在5种主要的分子亚型。两个主要的亚型是腔A和基本亚型，它们具有相反的特征，特别是存活率。为了更好地表征这两种亚型，希望更好地了解它们的不同生物学和临床结果，我们使用Affymetrix全基因组DNA微阵列对一系列138个肿瘤(80个管腔A和58个基底部)进行了分析。我们已经确定了5621个探针集，它们在我们的系列中的两个亚型之间有差异表达。这些差异在使用不同DNA微阵列平台的6个独立的公共系列(超过600个肿瘤)中得到了验证。对与这些探针组相关的功能和通路的分析，以及观察到的差异程度，证实了这两个亚型代表着非常不同的实体。与增殖、细胞周期、细胞运动、血管生成和NFkB信号相关的基因在基底肿瘤中高表达。涉及脂肪酸代谢、TGFb信号和雌激素受体(ER)信号的基因在鲁米那A样本中过度表达。在管腔肿瘤中过度表达的基因中有一半含有ER结合位点。差异表达基因的数量与区分2种不同解剖来源的癌症(乳腺癌和结肠癌)或区分急性髓系白血病和淋巴细胞性白血病的基因集一样多。我们提供了一份定义这两种亚型潜在诊断、预后和治疗靶点的基因/通路的综合清单，鉴于在分子水平上观察到的深刻差异，这些亚型应该得到不同的治疗。(C)2008年Wiley-Liss，Inc.
Heterogeneity of breast cancer makes its evolution difficult to predict, and its treatment far from being optimal. At least 5 main molecular subtypes exist. Two major subtypes are luminal A and basal subtypes, which have opposite features, notably survival. To characterize these 2 subtypes better, with the hope of better understanding their different biology and clinical outcome, we have profiled a series of 138 tumours (80 luminal A and 58 basal) using Affymetrix whole-genome DNA microarrays. We have identified 5,621 probe sets as differentially expressed between the 2 subtypes in our series. These differences were validated in 6 independent public series (more than 600 tumours) profiled using different DNA microarrays platforms. Analysis of functions and pathways related to these probe sets, and the extent of the observed differences, confirmed that the 2 subtypes represent very distinct entities. Genes associated with proliferation, cell cycle, cell motility, angiogenesis, and NFkB signalling were overexpressed in basal tumours. Genes involved in fatty acid metabolism, TGFB signalling, and oestrogen receptor (ER) signalling were overexpressed in luminal A samples. Half of the genes overexpressed in luminal tumours contained ER-binding sites. The number of differentially expressed genes was as high as the set of genes discriminating 2 cancers of different anatomical origin (breast and colon) or discriminating acute myeloid and lymphoid leukaemia. We provide a comprehensive list of genes/pathways that define potential diagnostic, prognostic and therapeutic targets for these 2 subtypes, which should be treated differently given the profound differences observed at the molecular level. (c) 2008 Wiley-Liss, Inc.