Crossing the LINE Toward Genomic Instability: LINE-1 Retrotransposition in Cancer

Jacqueline R Kemp,Michelle S Longworth

doi:10.3389/fchem.2015.00068

Jacqueline R Kemp, Michelle S Longworth

Open Access

https://doi.org/10.3389/fchem.2015.00068

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Abstract

Retrotransposons are repetitive DNA sequences that are positioned throughout the human genome. Retrotransposons are capable of copying themselves and mobilizing new copies to novel genomic locations in a process called retrotransposition. While most retrotransposon sequences in the human genome are incomplete and incapable of mobilization, the LINE-1 retrotransposon, which comprises~17% of the human genome, remains active. The disruption of cellular mechanisms that suppress retrotransposon activity is linked to the generation of aneuploidy, a potential driver of tumor development. When retrotransposons insert into a novel genomic region, they have the potential to disrupt the coding sequence of endogenous genes and alter gene expression, which can lead to deleterious consequences for the organism. Additionally, increased LINE-1 copy numbers provide more chances for recombination events to occur between retrotransposons, which can lead to chromosomal breaks and rearrangements. LINE-1 activity is increased in various cancer cell lines and in patient tissues resected from primary tumors. LINE-1 activity also correlates with increased cancer metastasis. This review aims to give a brief overview of the connections between LINE-1 retrotransposition and the loss of genome stability. We will also discuss the mechanisms that repress retrotransposition in human cells and their links to cancer.

Highlights

IntroductionRetrotransposons, a class of transposable elements (TE), are highly repetitive DNA sequences positioned throughout the human genome
Reviewed by: Revati Wani, Pfizer Inc., USA Sheila Lutz, Wadsworth Center, New York State Department of Health, USA
Increased Long interspersed nuclear elements (LINEs)-1 copy numbers provide more chances for recombination events to occur between retrotransposons, which can lead to chromosomal breaks and rearrangements

Summary

Introduction

Retrotransposons, a class of transposable elements (TE), are highly repetitive DNA sequences positioned throughout the human genome. These structural elements make use of an RNAmediated transposition process, allowing them to move from one location in the genome to another, while the original copy remains in its original locus. The human genome contains millions of copies of retrotransposons; only a single non-LTR retrotransposon family, the LINE-1 (L1) family, remains the primary source of LINE-1 and Genomic Instability retrotransposition. It was originally estimated that the average human diploid genome contains ∼80–100 active L1s that are capable of undergoing retrotransposition (Sassaman et al, 1997). A number of the newly inserted “hot” L1s were found to be extremely polymorphic and specific to a few individuals, suggesting that L1 retrotransposition may contribute to the propensity for one individual to develop disease over another (Beck et al, 2010; Huang et al, 2010; Iskow et al, 2010)

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