使用长读测序，课题组研究人员分析了10个具有异常高的反转录转位活性的肿瘤，包括6000多个体细胞事件。该课题组人员发现L1介导的反向易位经常发生，通常是由非同源染色体上的两个并发L1反转录转位事件驱动的。使用跨越低至高L1活性的独立肿瘤队列，该团队估计每60个体细胞逆转录转座子介导的重排发生一次事件。分子时间分析表明，这些事件发生在肿瘤发生的早期，确定L1活性是染色体不稳定的早期驱动因素。他们的发现表明，在某些肿瘤中，L1在癌症基因组进化中起着重要作用。
研究人员表示，LINE-1（L1）反转录转位在人类癌症中产生体细胞基因组变异，但短读测序限制了他们对其结构后果和动力学的理解。
附：英文原文
Title: Concurrent L1 retrotransposition events promote reciprocal translocations in human tumorigenesis
Author: Sonia Zumalave, Martin Santamarina, Nuria P. Espasandín, Jorge Zamora, Daniel Garcia-Souto, Javier Temes, Toby M. Baker, Jorge Rodríguez-Castro, Paula Otero, Ana Pequeo-Valtierra, Iago Otero, Ana Oitabén, Eva G. álvarez, Iria Díaz-Arias, Mónica Martínez-Fernández, Miguel G. Blanco, Peter Van Loo, Gael Cristofari, Bernardo Rodriguez-Martin, Jose M. C. Tubio
Issue&Volume: 2026-02-26
Abstract: LINE-1 (L1) retrotransposition generates somatic genomic variation in human cancer, but short-read sequencing has limited our understanding of its structural consequences and dynamics. Using long-read sequencing, we analyzed 10 tumors with exceptionally high retrotransposition activity, comprising over 6,000 somatic events. We reveal that L1-mediated reciprocal translocations occur frequently, typically driven by two concurrent L1 retrotransposition events on non-homologous chromosomes. Using an independent tumor cohort spanning low to high L1 activity, we estimate that retrotransposon-mediated rearrangements arise at a frequency of one event per 60 somatic retrotranspositions. Molecular timing analyses indicate that these events arise early in tumorigenesis, establishing L1 activity as an early driver of chromosomal instability. Our findings demonstrate that L1 contributes substantially to cancer genome evolution in certain tumors.
DOI: aee4513
Source: https://www.science.org/doi/10.1126/science.aee4513