The Role of Somatic L1 Retrotransposition in Human Cancers

doi:10.3390/v9060131

Review

. 2017 May 31;9(6):131.

doi: 10.3390/v9060131.

The Role of Somatic L1 Retrotransposition in Human Cancers

Emma C Scott^{1

2}, Scott E Devine^{3

4

5

6}

Affiliations

¹ Graduate Program in Molecular Medicine, University of Maryland, Baltimore, MD 21201, USA. escott@umaryland.edu.
² Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA. escott@umaryland.edu.
³ Graduate Program in Molecular Medicine, University of Maryland, Baltimore, MD 21201, USA. sdevine@som.umaryland.edu.
⁴ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA. sdevine@som.umaryland.edu.
⁵ Department of Medicine, University of Maryland School of Medicine; Baltimore, MD 21201, USA. sdevine@som.umaryland.edu.
⁶ Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. sdevine@som.umaryland.edu.

PMID: 28561751
PMCID: PMC5490808
DOI: 10.3390/v9060131

Review

The Role of Somatic L1 Retrotransposition in Human Cancers

Emma C Scott et al. Viruses. 2017.

. 2017 May 31;9(6):131.

doi: 10.3390/v9060131.

Authors

Emma C Scott^{1

2}, Scott E Devine^{3

4

5

6}

Affiliations

¹ Graduate Program in Molecular Medicine, University of Maryland, Baltimore, MD 21201, USA. escott@umaryland.edu.
² Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA. escott@umaryland.edu.
³ Graduate Program in Molecular Medicine, University of Maryland, Baltimore, MD 21201, USA. sdevine@som.umaryland.edu.
⁴ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA. sdevine@som.umaryland.edu.
⁵ Department of Medicine, University of Maryland School of Medicine; Baltimore, MD 21201, USA. sdevine@som.umaryland.edu.
⁶ Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. sdevine@som.umaryland.edu.

PMID: 28561751
PMCID: PMC5490808
DOI: 10.3390/v9060131

Abstract

The human LINE-1 (or L1) element is a non-LTR retrotransposon that is mobilized through an RNA intermediate by an L1-encoded reverse transcriptase and other L1-encoded proteins. L1 elements remain actively mobile today and continue to mutagenize human genomes. Importantly, when new insertions disrupt gene function, they can cause diseases. Historically, L1s were thought to be active in the germline but silenced in adult somatic tissues. However, recent studies now show that L1 is active in at least some somatic tissues, including epithelial cancers. In this review, we provide an overview of these recent developments, and examine evidence that somatic L1 retrotransposition can initiate and drive tumorigenesis in humans. Recent studies have: (i) cataloged somatic L1 activity in many epithelial tumor types; (ii) identified specific full-length L1 source elements that give rise to somatic L1 insertions; and (iii) determined that L1 promoter hypomethylation likely plays an early role in the derepression of L1s in somatic tissues. A central challenge moving forward is to determine the extent to which L1 driver mutations can promote tumor initiation, evolution, and metastasis in humans.

Keywords: LINE-1, L1; cancer genomics; retrotransposon; somatic retrotransposition.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Mobilization of L1s. New L1 insertions are generated via the five step process depicted here. This process begins with a full-length (FL)-L1 source element in the genomic DNA (A; colored bar; L1 features are not to scale). This element is transcribed (B) and the resulting mRNA (orange) is exported into the cytoplasm. This mRNA is translated (C) into the open reading frame (ORF)1p (light green) and ORF2p (dark green) proteins, which bind the L1 mRNA to form a ribonucleoprotein complex (D). This complex is imported (E) into the nucleus. Finally, the new L1 insertion is generated by target-primed reverse transcription (F). The result of this mobilization process is another copy of L1 (grey) located somewhere in the genome, flanked by target site duplications (TSDs; orange) and with a poly(A) tail (yellow) (G). UTR; untranslated region.

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References

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[1] Lander E.S., Linton L.M., Birren B., Nusbaum C., Zody M.C., Baldwin J., Devon K., Dewar K., Doyle M., FitzHugh W., et al. International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921. doi: 10.1038/35057062. - DOI - PubMed

[2] Lander E.S., Linton L.M., Birren B., Nusbaum C., Zody M.C., Baldwin J., Devon K., Dewar K., Doyle M., FitzHugh W., et al. International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921. doi: 10.1038/35057062. - DOI - PubMed

[3] McClintock B. The origin and behavior of mutable loci in maize. Proc. Natl. Acad. Sci. USA. 1950;36:344–355. doi: 10.1073/pnas.36.6.344. - DOI - PMC - PubMed

[4] McClintock B. The origin and behavior of mutable loci in maize. Proc. Natl. Acad. Sci. USA. 1950;36:344–355. doi: 10.1073/pnas.36.6.344. - DOI - PMC - PubMed

[5] Malik H.S., Burke W.D., Eickbush T.H. The age and evolution of non-LTR retrotransposable elements. Mol. Biol. Evol. 1999;16:793–805. doi: 10.1093/oxfordjournals.molbev.a026164. - DOI - PubMed

[6] Malik H.S., Burke W.D., Eickbush T.H. The age and evolution of non-LTR retrotransposable elements. Mol. Biol. Evol. 1999;16:793–805. doi: 10.1093/oxfordjournals.molbev.a026164. - DOI - PubMed

[7] Eickbush T.H., Malik H.S. Mobile DNA II. ASM Press; Washington, DC, USA: 2002. Origins and Evolution of Retrotransposons.

[8] Eickbush T.H., Malik H.S. Mobile DNA II. ASM Press; Washington, DC, USA: 2002. Origins and Evolution of Retrotransposons.

[9] Ostertag E.M., Kazazian H.H. Biology of mammalian L1 retrotransposons. Ann. Rev. Genet. 2001;35:501–538. doi: 10.1146/annurev.genet.35.102401.091032. - DOI - PubMed

[10] Ostertag E.M., Kazazian H.H. Biology of mammalian L1 retrotransposons. Ann. Rev. Genet. 2001;35:501–538. doi: 10.1146/annurev.genet.35.102401.091032. - DOI - PubMed

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The Role of Somatic L1 Retrotransposition in Human Cancers

Affiliations

The Role of Somatic L1 Retrotransposition in Human Cancers

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Affiliations

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Conflict of interest statement

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