Dhivya Sridaran, Premkumar Kumpati
Cancer Genetics and Nanomedicine Laboratory, Department of Biomedical Science, School of Basic Medical Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India.
Cancer Genetics and Nanomedicine Laboratory, Department of Biomedical Science, School of Basic Medical Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India.
Crit Rev Oncol Hematol. 2016 Feb;98:81-93. doi: 10.1016/j.critrevonc.2015.10.012. Epub 2015 Oct 31.
Chromosomal translocations as molecular signatures have been reported in various malignancies but, the mechanism behind which is largely unknown. Swapping of chromosomal fragments occurs by induction of double strand breaks (DSBs), most of which were initially assumed de novo. However, decoding of human genome proved that transposable elements (TE) might have profound influence on genome integrity. TEs are highly conserved mobile genetic elements that generate DSBs, subsequently resulting in large chromosomal rearrangements. Previously TE insertions were thought to be harmless, but recently gains attention due to the origin of spectrum of post-insertional genomic alterations and subsequent transcriptional alterations leading to development of deleterious effects mainly carcinogenesis. Though the existing knowledge on the cancer-associated TE dynamics is very primitive, exploration of underlying mechanism promises better therapeutic strategies for cancer. Thus, this review focuses on the prevalence of TE in the genome, associated genomic instability upon transposition activation and impact on tumorigenesis.
染色体易位作为分子特征已在多种恶性肿瘤中被报道，但其背后的机制在很大程度上尚不清楚。染色体片段的交换是由双链断裂（DSB）的诱导引起的，其中大多数最初被认为是从头产生的。然而，人类基因组的解码证明，转座元件（TE）可能对基因组完整性有深远影响。TE是高度保守的可移动遗传元件，可产生DSB，随后导致大规模染色体重排。以前认为TE插入是无害的，但最近由于插入后基因组改变谱的起源以及随后导致主要致癌作用等有害效应发展的转录改变而受到关注。尽管目前关于癌症相关TE动态的知识非常原始，但对潜在机制的探索有望为癌症带来更好的治疗策略。因此，本综述重点关注TE在基因组中的普遍性、转座激活后相关的基因组不稳定性及其对肿瘤发生的影响。
