Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
Science. 2011 Feb 4;331(6017):593-6. doi: 10.1126/science.1200801. Epub 2011 Jan 13.
Satellite repeats in heterochromatin are transcribed into noncoding RNAs that have been linked to gene silencing and maintenance of chromosomal integrity. Using digital gene expression analysis, we showed that these transcripts are greatly overexpressed in mouse and human epithelial cancers. In 8 of 10 mouse pancreatic ductal adenocarcinomas (PDACs), pericentromeric satellites accounted for a mean 12% (range 1 to 50%) of all cellular transcripts, a mean 40-fold increase over that in normal tissue. In 15 of 15 human PDACs, alpha satellite transcripts were most abundant and HSATII transcripts were highly specific for cancer. Similar patterns were observed in cancers of the lung, kidney, ovary, colon, and prostate. Derepression of satellite transcripts correlated with overexpression of the long interspersed nuclear element 1 (LINE-1) retrotransposon and with aberrant expression of neuroendocrine-associated genes proximal to LINE-1 insertions. The overexpression of satellite transcripts in cancer may reflect global alterations in heterochromatin silencing and could potentially be useful as a biomarker for cancer detection.
卫星重复序列位于异染色质中，可被转录为非编码 RNA，这些 RNA 与基因沉默和染色体完整性的维持有关。我们采用数字基因表达分析方法，发现这些转录本在小鼠和人类上皮性癌中过表达。在 10 例小鼠胰腺导管腺癌（PDAC）中，着丝粒周围卫星序列占所有细胞转录本的平均 12%（范围 1 至 50%），比正常组织中的表达增加了平均 40 倍。在 15 例人类 PDAC 中，α卫星转录本最为丰富，HSATII 转录本则对癌症具有高度特异性。在肺癌、肾癌、卵巢癌、结肠癌和前列腺癌中也观察到了类似的模式。卫星转录本的去抑制与长散布核元件 1（LINE-1）逆转录转座子的过度表达以及靠近 LINE-1 插入点的神经内分泌相关基因的异常表达相关。癌症中卫星转录本的过度表达可能反映了异染色质沉默的整体改变，并且可能作为癌症检测的生物标志物具有潜在的应用价值。
