Immune signatures correlate with L1 retrotransposition in gastrointestinal cancers

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Immune signatures correlate with L1 retrotransposition in gastrointestinal cancers

Long interspersed nuclear element-1 (L1) retrotransposons are normally suppressed in somatic tissues mainly by DNA methylation and antiviral defense. However, L1s can be desuppressed in cancers to act as insertional mutagens and cause genomic instability by creating DNA double strand breaks and chromosomal rearrangements. Whereas the frequency of somatic L1 insertions varies greatly among indiv...

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The Role of Somatic L1 Retrotransposition in Human Cancers

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 germ...

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Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution.

Somatic L1 retrotransposition events have been shown to occur in epithelial cancers. Here, we attempted to determine how early somatic L1 insertions occurred during the development of gastrointestinal (GI) cancers. Using L1-targeted resequencing (L1-seq), we studied different stages of four colorectal cancers arising from colonic polyps, seven pancreatic carcinomas, as well as seven gastric can...

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L1 retrotransposition

LINE-1 (L1) elements are the only active and autonomous transposable elements in humans. The core retrotransposition machinery is a ribonucleoprotein particle (RNP) containing the L1 mRNA, with endonuclease and reverse transcriptase activities. It initiates reverse transcription directly at genomic target sites upon endonuclease cleavage. Recently, using a direct L1 extension assay (DLEA), we s...

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DNA Damage and L1 Retrotransposition

Barbara McClintock was the first to suggest that transposons are a source of genome instability and that genotoxic stress assisted in their mobilization. The generation of double-stranded DNA breaks (DSBs) is a severe form of genotoxic stress that threatens the integrity of the genome, activates cell cycle checkpoints, and, in some cases, causes cell death. Applying McClintock's stress hypothes...

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ژورنال

عنوان ژورنال: Genome Research

سال: 2018

ISSN: 1088-9051,1549-5469

DOI: 10.1101/gr.231837.117