Genomics：非编码序列L1与癌症发生相关

Tlexander

英国研究人员日前报告说，人类基因组中一些“垃圾DNA”产生的物质与乳腺癌等癌症存在相关性，这项发现有助于研发新的癌症治疗方法。7 r: G4 @9 v( D2 ~! Q% L& d0 h6 H+ B
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英国诺丁汉大学等机构研究人员在美国《基因组学》杂志上报告说，他们发现人类基因组中名为L1的DNA序列会导致生成一些反常产物，而这些产物多见于乳腺癌细胞中。$ T1 l0 n/ p! H- L: `2 Q7 L
Genomics December 2009 doi:10.1016/j.ygeno.2009.08.013  6 m& \. R( @# q0 k1 o6 Z7 G! I
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Isolation of cancer-specific chimeric transcripts induced by hypomethylation of the LINE-1 antisense promoter* K6 a' b' y) O( @; t, L4 u0 F0 ^

. p3 F5 G( e5 m4 i( w! p- ]Hazel A. Cruickshanksa, b and Cristina Tufarelli, a, b, : ~: [5 y' n) B* e) k) X
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aWolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, UK
3 I! q, O0 E+ ^5 N+ Y: v9 @) Z5 A+ bbDepartment of Genetics, University of Leicester, Leicester, LE1 7RH, UK2 ~; a0 [1 r+ _8 C+ W7 a

% M# P, n. c" f% L% e% eThe antisense promoter of human LINE-1 (L1) retroelements can direct transcription of adjacent unique genomic sequences generating chimeric RNAs, which can perturb transcription of neighbouring genes. As L1 elements constitute 17% of the human genome, chimeric transcription is potentially widespread, but the extent to which this occurs is largely unknown. Using a genome-wide screen we have isolated novel chimeric transcripts that are unique to breast cancer cell lines, primary tumours and colon cancer cells. Expression of the cancer-specific chimeric transcripts can be induced in non-malignant breast epithelial cells by the demethylating drug 5-azacytidine. These findings indicate that loss of L1 methylation in cancer cells is linked to the expression of L1-chimeric transcripts which may therefore constitute a useful set of markers of malignancy.