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Genomics:非编码序列L1与癌症发生相关 [复制链接]

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发表于 2010-5-5 23:41 |只看该作者 |倒序浏览 |打印
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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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& N) _, c7 w2 i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。; ]; v; S3 L" N( _* i- E2 [* }
Genomics December 2009 doi:10.1016/j.ygeno.2009.08.013  * H$ x" G1 S8 a: n

0 u1 N; A7 V1 i0 G: TIsolation of cancer-specific chimeric transcripts induced by hypomethylation of the LINE-1 antisense promoter/ \* P; s8 A2 ?9 F2 ^* e

7 K5 F% p  j% B& a- Z4 l! h3 r1 XHazel A. Cruickshanksa, b and Cristina Tufarelli, a, b,
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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% R9 r$ c# P# A6 F8 H! ^) E5 l) k
bDepartment of Genetics, University of Leicester, Leicester, LE1 7RH, UK" L8 p1 m  ^" Q1 |" g. J
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The 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.
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