Zovoilis Athanasios, Mungall Andrew J, Moore Richard, Varhol Richard, Chu Andy, Wong Tina, Marra Marco, Jones Steven J M
BC Cancer Agency Genome Sciences Centre, Vancouver, BC, Canada.
EMBO Rep. 2014 Apr;15(4):402-10. doi: 10.1002/embr.201337950. Epub 2014 Feb 17.
Small non-coding RNAs (smRNAs) are known to be significantly enriched near the transcriptional start sites of genes. However, the functional relevance of these smRNAs remains unclear, and they have not been associated with human disease. Within the cancer genome atlas project (TCGA), we have generated small RNA datasets for many tumor types. In prior cancer studies, these RNAs have been regarded as transcriptional "noise," due to their apparent chaotic distribution. In contrast, we demonstrate their striking potential to distinguish efficiently between cancer and normal tissues and classify patients with cancer to subgroups of distinct survival outcomes. This potential to predict cancer status is restricted to a subset of these smRNAs, which is encoded within the first exon of genes, highly enriched within CpG islands and negatively correlated with DNA methylation levels. Thus, our data show that genome-wide changes in the expression levels of small non-coding RNAs within first exons are associated with cancer.
已知小非编码RNA（smRNA）在基因转录起始位点附近显著富集。然而，这些smRNA的功能相关性仍不清楚，且它们尚未与人类疾病相关联。在癌症基因组图谱计划（TCGA）中，我们已针对多种肿瘤类型生成了小RNA数据集。在先前的癌症研究中，由于这些RNA明显的混乱分布，它们被视为转录“噪音”。相比之下，我们证明了它们在有效区分癌症组织和正常组织以及将癌症患者分类到具有不同生存结果的亚组方面具有惊人的潜力。这种预测癌症状态的潜力仅限于这些smRNA的一个子集，该子集在基因的第一个外显子内编码，在CpG岛内高度富集，并且与DNA甲基化水平呈负相关。因此，我们的数据表明，第一个外显子内小非编码RNA表达水平的全基因组变化与癌症相关。
