Ponomaryova Anastasia A, Rykova Elena Y, Gervas Polina A, Cherdyntseva Nadezhda V, Mamedov Ilgar Z, Azhikina Tatyana L
Cancer Research Institute, Tomsk National Research Medical Center, 634009 Tomsk, Russia.
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Cells. 2020 Sep 2;9(9):2017. doi: 10.3390/cells9092017.
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.
尽管在过去十年中癌症的诊断和治疗取得了重大进展，但癌症仍然是人类死亡的主要原因之一。逆转录转座子的大量低甲基化，特别是LINE-1，被认为是大多数恶性转化的标志，因为它会导致逆转录元件的重新激活和随后的基因组不稳定。关于不同肿瘤类型中LINE-1异常甲基化的累积数据表明其在癌症发生和发展中具有重要作用。然而，LINE-1激活可作为癌症生物标志物的直接证据仍然有限。本综述的目的是批判性地评估已发表的关于LINE-1甲基化状态在癌症中的诊断/预后潜力的结果。我们的分析表明，LINE-1低甲基化是癌症发展的一个有前景的候选生物标志物，然而，它需要在临床和实验室研究中进行验证，以确认其对不同癌症类型和/或阶段的适用性。由于LINE-1在血液中有多个游离拷贝，就将其甲基化状态用作游离DNA液体活检的表观遗传癌症生物标志物而言，它比单拷贝基因具有优势。
