The Role of Somatic L1 Retrotransposition in Human CancersReportar como inadecuado


The Role of Somatic L1 Retrotransposition in Human Cancers


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1

Graduate Program in Molecular Medicine, University of Maryland, Baltimore, MD 21201, USA

2

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA

3

Department of Medicine, University of Maryland School of Medicine; Baltimore, MD 21201, USA

4

Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA





*

Author to whom correspondence should be addressed.



Academic Editors: David J. Garfinkel and Katarzyna J. Purzycka

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. View Full-Text

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





Autor: Emma C. Scott 1,2 and Scott E. Devine 1,2,3,4,*

Fuente: http://mdpi.com/



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