Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers.
Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers.
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DOI：
10.1126/science.1200801
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发表时间：
2011-02-04
期刊：
影响因子：
--
通讯作者：
Haber DA
中科院分区：
文献类型：
--
作者：
Ting DT;Lipson D;Paul S;Brannigan BW;Akhavanfard S;Coffman EJ;Contino G;Deshpande V;Iafrate AJ;Letovsky S;Rivera MN;Bardeesy N;Maheswaran S;Haber DA
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.
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