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Transcriptional landscape of PTEN loss in primary prostate cancer
bioRxiv - Cancer Biology Pub Date : 2020-10-09 , DOI: 10.1101/2020.10.08.332049
Eddie Luidy Imada , Diego Fernando Sanchez , Wikum Dinalankara , Thiago Vidotto , Ericka M Ebot , Svitlana Tyekucheva , Gloria Regina Franco , Lorelei Mucci , Massimo Loda , Edward M Schaeffer , Tamara Lotan , Luigi Marchionni

PTEN is the most frequently lost tumor suppressor in primary prostate cancer (PCa) and its loss is associated with aggressive disease. However, the transcriptional changes associated with PTEN loss in PCa have not been described in detail. Here, we applied a meta-analysis approach, leveraging two large PCa cohorts with experimentally validated PTEN and ERG status, to derive a transcriptomic signature of PTEN loss, while also accounting for potential confounders due to ERG rearrangements. Strikingly, the signature indicates a strong activation of both innate and adaptive immune systems upon PTEN loss, as well as an expected activation of cell-cycle genes. Moreover, we made use of our recently developed FC-R2 expression atlas to expand this signature to include many non-coding RNAs recently annotated by the FANTOM consortium. With this resource, we analyzed the TCGA-PRAD cohort, creating a comprehensive transcriptomic landscape of PTEN loss in PCa that comprises both the coding and an extensive non-coding counterpart.

中文翻译:

在原发性前列腺癌中PTEN丢失的转录情况

PTEN是原发性前列腺癌(PCa)中最常丢失的肿瘤抑制剂,其丢失与侵袭性疾病相关。然而,尚未详细描述与PCa中PTEN缺失相关的转录变化。在这里,我们采用了荟萃分析方法,利用两个大型PCa队列并通过实验验证了PTEN和ERG的状态,得出了PTEN丢失的转录组特征,同时也考虑了由于ERG重排而引起的潜在混杂因素。引人注目的是,该标记表明在PTEN缺失后先天免疫系统和适应性免疫系统均会强烈激活,以及预期的细胞周期基因激活。此外,我们利用了我们最近开发的FC-R2表达图谱来扩展此标记,使其包括FANTOM财团最近注释的许多非编码RNA。有了这个资源,
更新日期:2020-10-11
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