The Molecular Taxonomy of Primary Prostate Cancer.
The Molecular Taxonomy of Primary Prostate Cancer.
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DOI：
10.1016/j.cell.2015.10.025
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发表时间：
2015-11-05
期刊：
影响因子：
64.5
通讯作者：
Cancer Genome Atlas Research Network
中科院分区：
文献类型：
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作者：
Cancer Genome Atlas Research Network
原发性前列腺癌之间存在实质性异质性，这在分子异常谱及其可变的临床过程中是显而易见的。作为癌症基因组图谱（TCGA）的一部分，我们对333例原发性前列腺癌进行了全面的分子分析。我们的研究结果揭示了一种分子分类学，其中74%的这些肿瘤属于由特定基因融合（ERG，ETV 1/4，FLI 1）或突变（SPOP，FOXA 1，IDH 1）定义的七种亚型之一。表观遗传图谱显示出很大的异质性，包括IDH 1突变亚群与甲基化表型。雄激素受体（AR）活性变化很大，并以亚型特异性的方式与SPOP和FOXA 1突变肿瘤具有最高水平的AR诱导的转录。25%的前列腺癌在PI 3 K或MAPK信号通路中存在假定的可操作病变，19%的DNA修复基因失活。我们的分析揭示了原发性前列腺癌之间的分子异质性，以及潜在的可操作的分子缺陷。
There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, FLI1) or mutations (SPOP, FOXA1, IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1-mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.