基因君官网
2015年7月14日 讯 /生物谷BIOON/– 英国剑桥大学癌症研究中心的科学家们最近发现，在超过四分之三食道癌病例中，都有“跳跃基因”在增加遗传基因的混乱。他们用前沿技术读取了43例食管肿瘤和血液样品的DNA谱，分析出了这些可移动的遗传序列的跳跃程度。研究发表在最近的BMC Genomics。
“跳跃基因”，称为L1元素，可以自己连根拔起，并移动到新的DNA序列中，有时会不小心跳进控制细胞生长的基因中。本文主要作者Paul Edwards教授说：“这些跳跃基因在癌症细胞中“玩跳房子”的兴奋程度比在正常细胞中高得多。”研究人员将肿瘤样品的序列通过末端配测序（Paired-end sequencing）的方法，与参考基因组匹配序列中的异常之处。他们发现的证据表明，跳跃在每个肿瘤样品当中平均发生大约100次，在某一些肿瘤中它甚至发生700次。如果跳跃在或接近控制细胞生长的重要基因中，就会出现严重后果：改变基因的正常工作，让细胞生长和分裂失控，可能导致癌症。
英国癌症研究中心的Kat Arney教授评价说：“食道癌是最难治疗的一种癌症，我们正在致力于资助更多的研究，以找出其根本原因。这个新发现揭示更多关于遗传信息混乱与食管肿瘤的关系，有朝一日或许帮助开发更好的方法来诊断，治疗和监控这种疾病。”
研究表明，跳跃基因活动增强也发生在肺和肠道癌症中。所以了解细胞为何和如何做到这一点是至关重要的，或许与治疗癌症的新方法有关。 (基因宝jiyinbao.com)
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DOI:10.1186/s12864-015-1685-z
PMC
PMID
Mobile element insertions are frequent in oesophageal adenocarcinomas and can mislead paired-end sequencing analysis
Anna L. Paterson, Jamie M.J. Weaver, Matthew D. Eldridge, Simon Tavaré, Rebecca C. Fitzgerald, Paul A.W. Edwards and the OCCAMs Consortium
Abstract
Background
Mobile elements are active in the human genome, both in the germline and cancers, where they can mutate driver genes.
Results
While analysing whole genome paired-end sequencing of oesophageal adenocarcinomas to find genomic rearrangements, we identified three ways in which new mobile element insertions appear in the data, resembling translocation or insertion junctions: inserts where unique sequence has been transduced by an L1 (Long interspersed element 1) mobile element; novel inserts that are confidently, but often incorrectly, mapped by alignment software to L1s or polyA tracts in the reference sequence; and a combination of these two ways, where different sequences within one insert are mapped to different loci. We identified nine unique sequences that were transduced by neighbouring L1s, both L1s in the reference genome and L1s not present in the reference. Many of the resulting inserts were small fragments that include little or no recognisable mobile element sequence. We found 6 loci in the reference genome to which sequence reads from inserts were frequently mapped, probably erroneously, by alignment software: these were either L1 sequence or particularly long polyA runs. Inserts identified from such apparent rearrangement junctions averaged 16 inserts/tumour, range 0–153 insertions in 43 tumours. However, many inserts would not be detected by mapping the sequences to the reference genome, because they do not include sufficient mappable sequence. To estimate total somatic inserts we searched for polyA sequences that were not present in the matched normal or other normals from the same tumour batch, and were not associated with known polymorphisms. Samples of these candidate inserts were verified by sequencing across them or manual inspection of surrounding reads: at least 85 % were somatic and resembled L1-mediated events, most including L1Hs sequence. Approximately 100 such inserts were detected per tumour on average (range zero to approximately 700).
Conclusions
Somatic mobile elements insertions are abundant in these tumours, with over 75 % of cases having a number of novel inserts detected. The inserts create a variety of problems for the interpretation of paired-end sequencing data.