Analysis of gene expression in a developmental context emphasizes distinct biological leitmotifs in human cancers.
Analysis of gene expression in a developmental context emphasizes distinct biological leitmotifs in human cancers.
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DOI：
10.1186/gb-2008-9-7-r108
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发表时间：
2008
期刊：
影响因子：
12.3
通讯作者：
Kohane IS
中科院分区：
文献类型：
--
作者：
Naxerova K;Bult CJ;Peaston A;Fancher K;Knowles BB;Kasif S;Kohane IS
对肿瘤和发育转录组之间关系的系统分析提供了癌症基因表达全球趋势的概述。近年来，长期观察到的肿瘤组织和未成熟组织之间的相似性的分子基础已经开始出现。全基因组转录谱揭示了在几种肿瘤类型及其起源组织的早期发育阶段相似的基因表达特征。然而，目前尚不清楚这种关系是否是恶性肿瘤的普遍特征，不同肿瘤类型的发育成分是否存在异质性，以及癌症和发育之间的相似性在多大程度上是一种组织特异性现象。我们通过总结10个发展时间过程的主要特征来定义一个发展景观，并将各种人类肿瘤类型的基因表达投射到这一景观上。这一比较表明，在广泛的肿瘤中，在不同的甚至非同源的发育背景下，发育基因表达有明显的印记。我们的分析揭示了三种具有不同发育转录模式的癌症。我们描述了主导这些类别的生物学过程，并验证了关于小鼠胚胎肺发育的新时间序列的类别区分。最后，我们确定了一组在大多数癌症中被上调的基因，并表明这一特征在早期发展中是活跃的。对数十种组织中肿瘤和发育转录组之间关系的系统和定量概述，为癌症基因表达的全球趋势提供了可靠的轮廓，揭示了不同癌症类型中基因表达的潜在临床相关差异，并为解释小规模功能研究提供了参考框架。
A systematic analysis of the relationship between the neoplastic and developmental transcriptome provides an outline of global trends in cancer gene expression. In recent years, the molecular underpinnings of the long-observed resemblance between neoplastic and immature tissue have begun to emerge. Genome-wide transcriptional profiling has revealed similar gene expression signatures in several tumor types and early developmental stages of their tissue of origin. However, it remains unclear whether such a relationship is a universal feature of malignancy, whether heterogeneities exist in the developmental component of different tumor types and to which degree the resemblance between cancer and development is a tissue-specific phenomenon. We defined a developmental landscape by summarizing the main features of ten developmental time courses and projected gene expression from a variety of human tumor types onto this landscape. This comparison demonstrates a clear imprint of developmental gene expression in a wide range of tumors and with respect to different, even non-cognate developmental backgrounds. Our analysis reveals three classes of cancers with developmentally distinct transcriptional patterns. We characterize the biological processes dominating these classes and validate the class distinction with respect to a new time series of murine embryonic lung development. Finally, we identify a set of genes that are upregulated in most cancers and we show that this signature is active in early development. This systematic and quantitative overview of the relationship between the neoplastic and developmental transcriptome spanning dozens of tissues provides a reliable outline of global trends in cancer gene expression, reveals potentially clinically relevant differences in the gene expression of different cancer types and represents a reference framework for interpretation of smaller-scale functional studies.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
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
影响因子：
4.8
作者：
Otu, Hasan H.;Naxerova, Kamila;Karp, Seth J.
通讯作者：
Karp, Seth J.
影响因子：
64.8
作者：
Andang, Michael;Hjerling-Leffler, Jens;Ernfors, Patrik
通讯作者：
Ernfors, Patrik
影响因子：
64.8
作者：
Karnoub, Antoine E.;Dash, Ajeeta B.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.