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The methylation state of LINE\u20101 is often used as an indicator of global DNA methylation levels and it regulates the retrotransposition and somatic insertion of the genetic element. We have previously reported the significant relationship between LINE\u20101 hypomethylation and poor prognosis in upper gastrointestinal (GI) cancers. However, the causal relationships between LINE\u20101 hypomethylation, retrotransposition, and tumor\u2010specific insertion in upper GI cancers remain unknown. We used bisulfite\u2010pyrosequencing and quantitative real\u2010time PCR to verify LINE\u20101 methylation and copy number in tissue samples of 101 patients with esophageal and 103 patients with gastric cancer. Furthermore, we analyzed the LINE\u20101 retrotransposition profile with an originally developed L1Hs\u2010seq. In tumor samples, LINE\u20101 methylation levels were significantly lower than non\u2010tumor controls, while LINE\u20101 copy numbers were markedly increased. As such, there was a significant inverse correlation between the LINE\u20101 methylation level and copy number in tumor tissues, with lower LINE\u20101 methylation levels corresponding to higher LINE\u20101 copy numbers. Of particular importance is that somatic LINE\u20101 insertions were more numerous in tumor than normal tissues. Furthermore, we observed that LINE\u20101 was inserted evenly across all chromosomes, and most often within genomic regions associated with tumor\u2010suppressive genes. LINE\u20101 hypomethylation in upper GI cancers is related to increased LINE\u20101 retrotransposition and tumor\u2010specific insertion events, which may collectively contribute to the acquisition of aggressive tumor features through the inactivation of tumor\u2010suppressive genes.<\/jats:p>","DOI":"10.1111\/cas.16007","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T02:19:28Z","timestamp":1701137968000},"page":"247-256","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["<scp>LINE<\/scp>\n                    \u20101 hypomethylation, increased retrotransposition and tumor\u2010specific insertion in upper gastrointestinal cancer"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3657-2388","authenticated-orcid":false,"given":"Yoshifumi","family":"Baba","sequence":"first","affiliation":[{"name":"Department of Gastroenterological Surgery, 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