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.

Cancer Research Institute Tomsk National Research Medical Center 634009 Tomsk Russia

Central European Institute of Technology Masaryk University 625 00 Brno Czech Republic

Department of Engineering Issues in Ecology Novosibirsk State Technical University 630073 Novosibirsk Russia

Institute of Chemical Biology and Fundamental Medicine Siberian Division of the Russian Academy of Sciences 630090 Novosibirsk Russia

Laboratory of Molecular Pathophysiology 5 1 Kulakov National Medical Research Center for Obsterics 117997 Moscow Russia

Shemyakin Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences 117997 Moscow Russia

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