在人类乳腺癌中可移植元素的替代拼接
Alex Nesta1,2, Diogo F T Veiga3, Jacques Banchereau4,5
1The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA. alex.v.nesta@gmail.com.
Mobile DNA
|February 22, 2025
概括
可移植元素 (TE) 通过创造新的基因异型和改变基因表达,显著影响乳腺癌. 这些TE驱动的变化影响瘤的发展和患者的存活率,提供潜在的生物标志物.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 可转移元素 (TE) 是移动DNA序列,影响基因组进化和基因调节.
- 对TEs的失调与包括乳腺癌在内的各种癌症有关,可能导致瘤特异性的转录基因变化.
- 要了解TE影响的全部范围,需要进行全面的转录基因分析.
研究的目的:
- 用长读RNA测序研究可移植元素对乳腺癌转录组的综合影响.
- 识别和描述TE衍生异型及其对乳腺癌中新型拼接事件的贡献.
- 探索TE媒介拼接事件与乳腺癌亚型,患者存活率和RNA编辑的关联.
主要方法:
- 利用长读RNA测序 (LR-seq) 来分析30个乳腺样本中的142,514个全长异型.
- 在1,135个乳腺瘤 (TCGA) 和1,329个健康组织 (GTEx) 中量化了TE重叠拼接事件.
- 识别了改变拼接的TE插入,并分析了全长异型中的RNA编辑签名.
主要成果:
- 大约50%的分析异构体含有TE序列,导致一半的新拼接连接.
- 发现了300个TE重叠,瘤特异性拼接事件,其中一些与特定的乳腺癌亚型 (例如HER2+瘤) 和患者生存率差有关.
- 识别了数千种具有RNA编辑特征的异构体,包括一种新的RHOA异构体,并验证了TE驱动的拼接变化.
结论:
- 失调的可转移元素对乳腺癌转录组具有广泛的影响,产生多种异型并改变基因表达.
- 长时间读取的异型序列测序对于揭示TE对癌症生物学的全部影响至关重要.
- 来自TE的异构体代表了潜在的新生物标志物和乳腺癌的治疗点.
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