2015年7月14日 訊 /生物谷BIOON/-- 英國劍橋大學癌症研究中心的科學家們最近發現，在超過四分之三食道癌病例中，都有「跳躍基因」在增加遺傳基因的混亂。他們用前沿技術讀取了43例食管腫瘤和血液樣品的DNA譜，分析出了這些可移動的遺傳序列的跳躍程度。研究發表在最近的BMC Genomics。
「跳躍基因」，稱為L1元素，可以自己連根拔起，並移動到新的DNA序列中，有時會不小心跳進控制細胞生長的基因中。本文主要作者Paul Edwards教授說：「這些跳躍基因在癌症細胞中「玩跳房子」的興奮程度比在正常細胞中高得多。」研究人員將腫瘤樣品的序列通過末端配測序（Paired-end sequencing）的方法，與參考基因組匹配序列中的異常之處。他們發現的證據表明，跳躍在每個腫瘤樣品當中平均發生大約100次，在某一些腫瘤中它甚至發生700次。如果跳躍在或接近控制細胞生長的重要基因中，就會出現嚴重後果：改變基因的正常工作，讓細胞生長和分裂失控，可能導致癌症。
英國癌症研究中心的Kat Arney教授評價說：「食道癌是最難治療的一種癌症，我們正在致力於資助更多的研究，以找出其根本原因。這個新發現揭示更多關於遺傳信息混亂與食管腫瘤的關係，有朝一日或許幫助開發更好的方法來診斷，治療和監控這種疾病。」
研究表明，跳躍基因活動增強也發生在肺和腸道癌症中。所以了解細胞為何和如何做到這一點是至關重要的，或許與治療癌症的新方法有關。 (生物谷Bioon.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.