L1 retrotransposons are the only protein-coding active transposable elements in the human genome. Although silenced during normal conditions, they are highly expressed in human epithelial cancers including high-grade serous ovarian cancer (HGSC), where they transcribe to form L1 mRNA and subsequently integrate into the genome by a process called retrotransposition. Despite of high L1 protein expression in the earliest phases of HGSC, these tumors do not accrue many somatic L1 insertions. To understand this unexplained disconnect, we monitored the transcription and retrotransposition activity of two frequently expressed retrotransposition-competent (RC)-L1 (RC-L1) in 64 clinical tumor specimens from 34 HGSC patients and found that despite the presence of RC-L1 mRNA, a third of samples did not acquire somatic L1 insertions. In addition to high inter-patient variability in retrotransposition frequency, there was remarkable intra-patient heterogeneity in L1 insertion patterns between tumor sites, indicating that L1 retrotransposition is highly dynamic in vivo. Comparison of genomic and transcriptomic features of L1-null tumors with L1-high tumors (those with ≥5 somatic L1 insertions) showed that retrotransposition was favored by increased rate of cell proliferation.

中文翻译：

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L1 逆转录转座在高级别浆液性卵巢癌中受到转录后调控

L1 反转录转座子是人类基因组中唯一的蛋白质编码活性转座因子。虽然在正常情况下沉默，但它们在人类上皮癌中高度表达，包括高级别浆液性卵巢癌 (HGSC)，在那里它们转录形成 L1 mRNA，随后通过称为逆转录转座的过程整合到基因组中。尽管在 HGSC 的早期阶段具有高 L1 蛋白表达，但这些肿瘤不会产生许多体细胞 L1 插入。为了理解这种无法解释的脱节，我们监测了来自 34 名 HGSC 患者的 64 个临床肿瘤标本中两种经常表达的反转录转座能力 (RC)-L1 (RC-L1) 的转录和反转录转座活性，发现尽管存在 RC-L1 mRNA ，三分之一的样本没有获得体细胞 L1 插入。除了患者间反转录转座频率的高变异性外，肿瘤部位之间的 L1 插入模式存在显着的患者内异质性，表明 L1 反转录转座在体内是高度动态的。比较 L1 无效肿瘤与 L1 高肿瘤（具有≥5 个体细胞 L1 插入的肿瘤）的基因组和转录组学特征表明，细胞增殖率增加有利于逆转录转座。