Somatic L1 retrotranspositions in normal human cells

Genomic mutations accumulate in normal cells during lifetime; however, somatic mosaicism generated by mobilization of transposable elements is not well understood. Here, we sequenced 880 normal colonic crypt, 12 colonic crypt from adenomatous polyp, and 19 colorectal cancers from 20 individuals. Most of the colorectal epithelial cells acquired somatic L1 retrotranspositions and the burden is ~10-fold increased in cancer tissues. Among 34 source elements in our cohort, 44% of them are new, often private in an individual, suggesting ongoing emergence of active L1 sources in humans. L1 insertion is more frequent during early embryogenesis period probably due to global hypomethylation. The hot L1s always contain demethylated promoters, suggesting the hypothesis that some L1s which accidentally avoid remethylation remain transcriptionally active and cause L1 retrotransposition events along the cellular lineages.EGA study EGAS00001006213