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。( Y7 Y- k. C0 j( X& v3 _
/ W5 a7 }2 o0 u+ S4 o$ t
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。( A( Q1 R& E  {6 ?9 ^* q# v+ |% y
Genomics December 2009 doi:10.1016/j.ygeno.2009.08.013  * r$ Z# y6 [- f( a* C/ x
0 l  J. |( B4 v+ D) ]- w/ g1 p) G: w6 t
Isolation of cancer-specific chimeric transcripts induced by hypomethylation of the LINE-1 antisense promoter1 U% u- y/ d( U/ Y( c6 \
2 D: [- T4 x1 T+ a
Hazel A. Cruickshanksa, b and Cristina Tufarelli, a, b, ! o6 u5 X. ]& J- {' J

- Q" w" \; H" F! i" waWolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, UK+ g. H! A1 a% P) o! ~- [" r
bDepartment of Genetics, University of Leicester, Leicester, LE1 7RH, UK
# @& d7 b* q8 k
3 t0 P. M! i. i8 U3 AThe 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.