Abstract 4101: Prognostic significance of LINE-1 mathylation level in gastric cancer

Iwagami, Shiro; Baba, Yoshifumi; Watanabe, Masayuki; Shigaki, Hironobu; Miyake, Keisuke; Kurashige, Jyunji; Ishimoto, Takatsugu; Iwatsuki, Masayuki; Baba, Hideo

doi:10.1158/1538-7445.am2012-4101

Cited by 1 publication

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“…Active TEs are considered highly mutagenic and are commonly linked to the multiple steps of cancer development and progression (14,(16)(17)(18). Moreover, L1 hypomethylation has been revealed in multiple cancer types, including lung cancer (19), colorectal cancer (20), breast cancer (21), prostate cancer (22), hepatocellular carcinoma (23), ovarian cancers (24) and esophageal squamous cell carcinoma (25), and was typically associated with poor clinical outcomes, likely due to resulting genome instability and presumed TE activation.…”

Section: Introductionmentioning

confidence: 99%

Mobile retroelements induced by hypomethylating agents are restricted to transpose in myeloid malignancies

Plevova,

Pavlova,

Krzyzankova

et al. 2023

Preprint

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Retroelements (RE) present in the human genome are silenced via multiple mechanisms, including DNA methylation, to prevent their potentially mutagenic effect. RE activity, demonstrated by their expression and somatic retrotransposition events, is deregulated in multiple tumor types but not in leukemia. We hypothesized that treatment with hypomethylating agents (HMA), commonly used in myelodysplastic syndromes and acute myeloid leukemia, could lead to increased RE activity and somatic retrotranspositions, and contribute to disease progression. We induced expression of ORF1p protein encoded by long interspersed nuclear element-1 (L1) after 72h treatment with HMA in DAMI and HL-60 cell lines. ORF1p was predominantly localized in the cytoplasm, as evidenced by fluorescent microscopy of the DAMI cell line. To study whether long-term HMA therapy may induce somatic retrotranspositions, we (i) treated both cell lines for four weeks, (ii) analyzed a cohort of 17 MDS patients before and on treatment with HMA. Using a previously established sensitive NGS-based method, no RE events were identified. To conclude, we show that although HMA induces the expression of L1-encoded proteins in tumor myeloid cell lines, de novo somatic retrotransposition events do not arise during the long-term treatment of MDS patients and myeloid cell lines with these agents.

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