Science：逆转录转座子在肿瘤发生中的重要作用

6月28日，Science杂志在线报道了关于体细胞逆转录转座子在人类肿瘤发生中作用的最新研究进展。

转座子（TEs）在人类基因组中含量丰富，有些能够通过RNA中间体产生新的插入序列。在癌症细胞中，通常抑制TE活动的机制如果遭到破坏，可能会促进诱导突变的逆转录转座子的产生。研究者对五个类型的癌症中 43个高覆盖率全基因组测序数据集的TE插入序列，进行了单个核苷酸分辨率的分析。

研究确定了194个高可信度TE插入序列，以及与之相应的正常基因组中，数千个多态性TE插入序列。体细胞插入序列存在于上皮性肿瘤，而不在血液或脑肿瘤中。体细胞L1插入序列往往发生在癌症中常见的突变基因中。该插入序列破坏靶基因的表达，偏爱出现于癌症特异性DNA低甲基化的区域。这些现象表明，体细胞L1插入序列在肿瘤发生的潜在的重要影响。

doi:10.1016/j.cell.2011.10.017
PMC:
PMID:

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.