Abstract
Cancer remains one of the main causes of human mortality despite significant progress in its diagnostics and therapy achieved in the past decade. Massive hypomethylation of retrotransposons, in particular LINE-1, is considered a hallmark of most malignant transformations as it results in the reactivation of retroelements and subsequent genomic instability. Accumulating data on LINE-1 aberrant methylation in different tumor types indicates its significant role in cancer initiation and progression. However, direct evidence that LINE-1 activation can be used as a cancer biomarker is still limited. The objective of this review was to critically evaluate the published results regarding the diagnostic/prognostic potential of the LINE-1 methylation status in cancer. Our analysis indicates that LINE-1 hypomethylation is a promising candidate biomarker of cancer development, which, however, needs validation in both clinical and laboratory studies to confirm its applicability to different cancer types and/or stages. As LINE-1 is present in multiple cell-free copies in blood, it has advantages over single-copy genes regarding perspectives of using its methylation status as an epigenetic cancer biomarker for cell-free DNA liquid biopsy.
Highlights
The fifth base, noncanonical 5-methyl-cytosine, was added to the four canonical ones by RollinHotchkiss in 1948 [1]
DNA methylation is a key mechanism for repression of transposons—mobile elements which occupy about half of the human genome
Table1.1.L1 L1 hypomethylation is proposed to be an initiating factor in carcinogenesis because, hypomethylation is proposed to be an initiating factor in carcinogenesis because, in some in some cancers, significant demethylation is observed in premalignant lesions before cancer cancers, significant demethylation is observed in premalignant lesions before cancer transformation
Summary
The fifth base, noncanonical 5-methyl-cytosine, was added to the four canonical ones by Rollin. Hotchkiss in 1948 [1] This chemical modification occurs almost exclusively in the context of cytosine base linked to guanosine, termed CpG. DNA methylation is a key mechanism for repression of transposons—mobile elements which occupy about half of the human genome. Hypermethylation of CpG sites in the promoter region of onco-suppressor genes could modify the spatial structure of chromatin, causing transcriptional repression. Different genomic hypomethylation and hypermethylation patterns are characteristic for particular cancer types (the recent meta-analysis is presented in [13]). These patterns could serve as diagnostic and prognostic biomarkers in various analyses, including noninvasive tests such as liquid biopsy [14]. Global genome hypomethylation observed in repetitive sequences and intergenic regions, is one of the hallmarks of cancer cells [15], and is suggested to promote oncogenesis by increasing the mobility of transposons, that leads to genomic instability [16,17,18,19,20]
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