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。 9 k' K; G+ l0 r! Z5 Z4 ?4 C * A' J5 ?8 {7 z* v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。& O; f' y/ O" k$ I0 W5 q, u. ^ A2 i
Genomics December 2009 doi:10.1016/j.ygeno.2009.08.013 5 R5 ^# Z" I# s
6 L( v, Z% b! E' p6 y; sIsolation of cancer-specific chimeric transcripts induced by hypomethylation of the LINE-1 antisense promoter5 C4 v* o8 u- m& o
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Hazel A. Cruickshanksa, b and Cristina Tufarelli, a, b, 7 `$ Z8 P8 b5 T7 d. }5 t
) n& W0 a( P- q: L5 taWolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, UK$ `# `% n& C; M& G' o6 x, D
bDepartment of Genetics, University of Leicester, Leicester, LE1 7RH, UK - H- F- _& }- v$ s & G' |* I/ }) [2 W, y5 VThe 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.