6月28日，Science雜志在線報(bào)道了關(guān)于體細(xì)胞逆轉(zhuǎn)錄轉(zhuǎn)座子在人類腫瘤發(fā)生中作用的最新研究進(jìn)展,。
轉(zhuǎn)座子（TEs）在人類基因組中含量豐富，有些能夠通過RNA中間體產(chǎn)生新的插入序列,。在癌癥細(xì)胞中,，通常抑制TE活動(dòng)的機(jī)制如果遭到破壞，可能會促進(jìn)誘導(dǎo)突變的逆轉(zhuǎn)錄轉(zhuǎn)座子的產(chǎn)生,。研究者對五個(gè)類型的癌癥中 43個(gè)高覆蓋率全基因組測序數(shù)據(jù)集的TE插入序列,，進(jìn)行了單個(gè)核苷酸分辨率的分析,。
研究確定了194個(gè)高可信度TE插入序列，以及與之相應(yīng)的正?；蚪M中,，數(shù)千個(gè)多態(tài)性TE插入序列。體細(xì)胞插入序列存在于上皮性腫瘤,，而不在血液或腦腫瘤中,。體細(xì)胞L1插入序列往往發(fā)生在癌癥中常見的突變基因中。該插入序列破壞靶基因的表達(dá),，偏愛出現(xiàn)于癌癥特異性DNA低甲基化的區(qū)域,。這些現(xiàn)象表明，體細(xì)胞L1插入序列在腫瘤發(fā)生的潛在的重要影響,。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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Landscape of Somatic Retrotransposition in Human Cancers
Eunjung Lee1,2, Rebecca Iskow3, Lixing Yang1, Omer Gokcumen3, Psalm Haseley1,2, Lovelace J. Luquette III1, Jens G. Lohr4,5, Christopher C. Harris6, Li Ding6, Richard K. Wilson6, David A. Wheeler7, Richard A. Gibbs7, Raju Kucherlapati2,8, Charles Lee3, Peter V. Kharchenko1,9,*, Peter J. Park1,2,9,*, The Cancer Genome Atlas Research Network
Transposable elements (TEs) are abundant in the human genome, and some are capable of generating new insertions through RNA intermediates. In cancer, the disruption of cellular mechanisms that normally suppress TE activity may facilitate mutagenic retrotranspositions. We performed single-nucleotide resolution analysis of TE insertions in 43 high-coverage whole-genome sequencing data sets from five cancer types. We identified 194 high-confidence somatic TE insertions, as well as thousands of polymorphic TE insertions in matched normal genomes. Somatic insertions were present in epithelial tumors but not in blood or brain cancers. Somatic L1 insertions tend to occur in genes that are commonly mutated in cancer, disrupt the expression of the target genes, and are biased toward regions of cancer-specific DNA hypomethylation, highlighting their potential impact in tumorigenesis.
