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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。0 z. a0 E. r3 A9 V& s. D( n
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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。
2 C( A+ z$ Y* w- e, k- o2 F9 eGenomics December 2009 doi:10.1016/j.ygeno.2009.08.013
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5 Q* b) x& W" H6 d2 a9 v- C5 aIsolation of cancer-specific chimeric transcripts induced by hypomethylation of the LINE-1 antisense promoter
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Hazel A. Cruickshanksa, b and Cristina Tufarelli, a, b, ( d! g3 z0 D2 W" U
; l" k( K0 `* l, P; H: K- OaWolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, UK% k# {) Y. P$ X9 d
bDepartment of Genetics, University of Leicester, Leicester, LE1 7RH, UK
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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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