早期黑色素瘤中的侵袭转移驱动因子是致癌基因。
Proinvasion metastasis drivers in early-stage melanoma are oncogenes.
机构信息
Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
出版信息
Cancer Cell. 2011 Jul 12;20(1):92-103. doi: 10.1016/j.ccr.2011.05.025.
Abstract
Clinical and genomic evidence suggests that the metastatic potential of a primary tumor may be dictated by prometastatic events that have additional oncogenic capability. To test this "deterministic" hypothesis, we adopted a comparative oncogenomics-guided function-based strategy involving: (1) comparison of global transcriptomes of two genetically engineered mouse models with contrasting metastatic potential, (2) genomic and transcriptomic profiles of human melanoma, (3) functional genetic screen for enhancers of cell invasion, and (4) evidence of expression selection in human melanoma tissues. This integrated effort identified six genes that are potently proinvasive and oncogenic. Furthermore, we show that one such gene, ACP5, confers spontaneous metastasis in vivo, engages a key pathway governing metastasis, and is prognostic in human primary melanomas.
摘要
临床和基因组证据表明，原发肿瘤的转移潜能可能由具有额外致癌能力的促转移事件决定。为了验证这一“确定性”假说，我们采用了一种基于比较肿瘤基因组学的功能导向策略，包括：（1）比较两种遗传工程小鼠模型的全局转录组，这两种模型具有不同的转移潜能；（2）人类黑色素瘤的基因组和转录组特征；（3）细胞侵袭增强子的功能遗传筛选；（4）人类黑色素瘤组织中表达选择的证据。这项综合研究确定了六个具有强大侵袭性和致癌性的基因。此外，我们还表明，其中一个基因 ACP5 在体内赋予自发转移能力，参与调控转移的关键途径，并在人类原发性黑色素瘤中具有预后意义。
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