L1 Retrotransposition in Normal Colorectal Epithelium

Abstract

Somatic L1 retrotransposition refers to the process in which long interspersed nuclear elements (LINE-1 or L1 elements), which are a type of transposable element, move within the DNA of somatic cells. These elements can have the ability to "copy and paste" themselves into different genomic locations, potentially leading to genetic alterations. While L1 retrotransposition has been extensively studied in the context of cancer, it is still a topic of ongoing research to determine its prevalence and significance in normal tissues, including the colorectal epithelium. Colorectal epithelium refers to the tissue lining the colon and rectum, and abnormalities in this tissue can contribute to the development of colorectal cancer. Nam and colleagues explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals. They found 1,708 somatic L1 retrotrans position events that were enriched in the colorectal epithelium and showed a positive relationship with age. Analysis of matched cancers further suggested that the somatic L1 retrotransposition rate is substantially increased during colorectal tumorigenesis. They concluded that L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime. Nature. 2023 May;617(7961):540-547.  doi: 10.1038/s41586-023-06046-z.