Genomics：非编码序列L1与癌症发生相关

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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。
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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。; {# K" A4 }& W% N) x% p5 M1 P
Genomics December 2009 doi:10.1016/j.ygeno.2009.08.013  ' t( T5 F, u, V8 J$ Q4 _5 j5 p
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Isolation of cancer-specific chimeric transcripts induced by hypomethylation of the LINE-1 antisense promoter5 G& L8 c( t: R( [/ d# T

* p* v5 C8 P; P" JHazel A. Cruickshanksa, b and Cristina Tufarelli, a, b, 9 \$ I6 `, E, L; ~

1 ~* x- n  R& l4 b5 ^aWolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, UK
2 M) \3 I" B2 x, ]bDepartment of Genetics, University of Leicester, Leicester, LE1 7RH, UK/ ?! _+ y0 d, p& ^& J! O

! g* |2 Z0 T/ 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.