Aberrant Methylation of LINE-1 Transposable Elements: A Search for Cancer Biomarkers

Cells. 2020 Sep 2;9(9):2017. doi: 10.3390/cells9092017.

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.

Keywords: DNA methylation; LINE-1 (L1); cell-free DNA; epigenetic cancer biomarker.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Cell-Free Nucleic Acids / blood
  • Cell-Free Nucleic Acids / genetics*
  • DNA Methylation
  • DNA Transposable Elements*
  • Disease Progression
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic*
  • Genomic Instability
  • Humans
  • Liquid Biopsy
  • Long Interspersed Nucleotide Elements*
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / mortality
  • Prognosis
  • Signal Transduction
  • Survival Analysis

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • DNA Transposable Elements