Frontiers in Cell and Developmental Biology (Dec 2021)

Deoxyribonucleic Acid 5-Hydroxymethylation in Cell-Free Deoxyribonucleic Acid, a Novel Cancer Biomarker in the Era of Precision Medicine

  • Ling Xu,
  • Ling Xu,
  • Yixin Zhou,
  • Lijie Chen,
  • Abdul Saad Bissessur,
  • Abdul Saad Bissessur,
  • Jida Chen,
  • Misha Mao,
  • Misha Mao,
  • Siwei Ju,
  • Siwei Ju,
  • Lini Chen,
  • Lini Chen,
  • Cong Chen,
  • Cong Chen,
  • Zhaoqin Li,
  • Zhaoqin Li,
  • Xun Zhang,
  • Xun Zhang,
  • Fei Chen,
  • Fei Chen,
  • Feilin Cao,
  • Linbo Wang,
  • Qinchuan Wang

DOI
https://doi.org/10.3389/fcell.2021.744990
Journal volume & issue
Vol. 9

Abstract

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Aberrant methylation has been regarded as a hallmark of cancer. 5-hydroxymethylcytosine (5hmC) is recently identified as the ten-eleven translocase (ten-eleven translocase)-mediated oxidized form of 5-methylcytosine, which plays a substantial role in DNA demethylation. Cell-free DNA has been introduced as a promising tool in the liquid biopsy of cancer. There are increasing evidence indicating that 5hmC in cell-free DNA play an active role during carcinogenesis. However, it remains unclear whether 5hmC could surpass classical markers in cancer detection, treatment, and prognosis. Here, we systematically reviewed the recent advances in the clinic and basic research of DNA 5-hydroxymethylation in cancer, especially in cell-free DNA. We further discuss the mechanisms underlying aberrant 5hmC patterns and carcinogenesis. Synergistically, 5-hydroxymethylation may act as a promising biomarker, unleashing great potential in early cancer detection, prognosis, and therapeutic strategies in precision oncology.

Keywords