{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T01:46:22Z","timestamp":1780710382060,"version":"3.54.1"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015501","name":"Qu\u1ef9 \u0110\u1ed5i m\u1edbi s\u00e1ng t\u1ea1o Vingroup","doi-asserted-by":"publisher","award":["VINIF.2022.DA00036"],"award-info":[{"award-number":["VINIF.2022.DA00036"]}],"id":[{"id":"10.13039\/501100015501","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The autonomous and active Long-Interspersed Element-1 (<jats:italic>LINE-1<\/jats:italic>, <jats:italic>L1<\/jats:italic>) and the non-autonomous <jats:italic>Alu<\/jats:italic> retrotransposon elements, contributing to 30% of the human genome, are the most abundant repeated sequences. With more than 90% of their sequences being methylated in normal cells, these elements undeniably contribute to the global DNA methylation level and constitute a major part of circulating-cell-free DNA (cfDNA). So far, the hypomethylation status of <jats:italic>LINE-1<\/jats:italic> and <jats:italic>Alu<\/jats:italic> in cellular and extracellular DNA has long been considered a prevailing hallmark of ageing-related diseases and cancer. This study demonstrated that errors in <jats:italic>LINE-1<\/jats:italic> and <jats:italic>Alu<\/jats:italic> methylation level measurements were caused by an excessive input quantity of genomic DNA used for bisulfite conversion. Using the minuscule DNA amount of 0.5 ng, much less than what has been used and recommended so far (500 ng-2 \u03bcg) or 1 \u03bcL of cfDNA extracted from 1 mL of blood, we revealed hypermethylation of <jats:italic>LINE-1<\/jats:italic> and <jats:italic>Alu<\/jats:italic> in 407 tumour samples of primary breast, colon and lung cancers when compared with the corresponding pair-matched adjacent normal tissue samples (P &lt; 0.05\u20130.001), and in cfDNA from 296 samples of lung cancers as compared with 477 samples from healthy controls (P &lt; 0.0001). More importantly, <jats:italic>LINE-1<\/jats:italic> hypermethylation in cfDNA is associated with healthy ageing. Our results have not only contributed to the standardized bisulfite-based protocols for DNA methylation assays, particularly in applications on repeated sequences but also provided another perspective for other repetitive sequences whose epigenetic properties may have crucial impacts on genome architecture and human health.<\/jats:p>","DOI":"10.1371\/journal.pone.0316394","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T18:40:52Z","timestamp":1735584052000},"page":"e0316394","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["An appropriate DNA input for bisulfite conversion reveals LINE-1 and Alu hypermethylation in tissues and circulating cell-free DNA from cancers"],"prefix":"10.1371","volume":"19","author":[{"given":"Trang Thi Quynh","family":"Tran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tung 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