Cancer, the Human Mobilome, and LINE-1 Retrotransposons

Essentially half of human DNA consists of repeated transposable elements or "mobile" DNA. One type of long interspersed element—LINE-1—is one of the most prevalent variants and accounts for approximately 17% of the human genome.


The LINE-1 sequence is a protein-coding transposable element that copies itself through an RNA intermediate—a retrotransposon. It addition to replicating itself, LINE-1 is also responsible for transposition of other non-autonomously mobile short interspersed elements (SINEs), such as ALU repeat sequences. Although frequently dismissed as non-consequential, these elements have profoundly affected our genetic make-up and appear to plan an important role in tumorigenesis, as the recent review article by Kathleen Burns from Johns Hopkins University describes.


In 1988, researchers found that two unrelated hemophilia patients had similar LINE-1 insertions. Since then, 124 instances of genetic diseases have been linked to germline LINE-1 retrotransposition. LINE-1 mobilization, then, can disrupt genetics during embryonic development and causes a small number of congenital abnormalities. While significant, however, its impact is relatively rare. What is more interesting is that recent work has also shown that, in many cancers, LINE-1 mobilization activity also spikes. Like during fetal development, LINE-1 activity may be an important driver of genetic instability in tumorigenesis and could provide an important indicator for prognosis, diagnosis, and malignancy.

LINE-1 sequences contain a RNA polymerase II promoter that is mostly shut down by methylation in normal tissue. This modification prevents autonomous retrotransposition However, in cancer cells, hypomethylation makes the LINE-1 promoter accessible, which activates these elements. While most LINE-1 insertions in cancers occur at intronic or intergenic regions where they might not be expected to disrupt genetics, the LINE-1 sequence, with its own promoter, can activate nearby genes, produce new RNA isoforms, break genes, or shuffle exons. Although there are several examples of these modifications, in fact, the role that these LINE-1 transpositions play in carcinogenesis remains mostly obscure and requires significantly more investigation.

To assist researchers interested in measuring LINE-1 activation, Cellecta recently launched the LINE-1 Mobile Element NGS Assay Kit--the first commercially available assay for assessing retrotransposon activity. This unique assay enables researchers to assess LINE-1 mobility and analyze the insertion sites of the element in genomic DNA isolated from tumors, blood, and cells. The kit contains the primers and enzymes to prepare samples for NGS and analysis.


Formation of a new DNA copy of LINE-1 transpositions, flanked by duplication of the target site


Institute of Biology and Medical Genetics of the First Faculty of Medicine of Charles University and the General Teaching Hospital, (2005-2006), Target primed reverse transcription (TPRT). Formation of a new DNA copy of L1, flanked by duplication of the target site [ONLINE]. Available at: [Accessed 3 July 2017].


Composition of the Human Genome


Genome Year Blog, (2016), Composition of the Human Genome [ONLINE]. Available at: [Accessed 3 July 2017].
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