國家衛生研究院 NHRI:Item 3990099045/10875
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    题名: Cyclin D1 promoter -56 and -54bp CpG un-methylation predicts invasive progression in arsenic-induced Bowen's disease
    作者: Liao, WT;You, HL;Chai, CY;Lee, CH;Lan, CE;Chang, SJ;Yu, CL;Yu, HS
    贡献者: National Institute of Environmental Health Sciences
    摘要: BACKGROUND: Patients with arsenic-induced Bowen's disease (As-BD) are at risk of developing invasive cancers in the skin, lung, and urinary bladder. However, a longitudinal follow-up study on the association between As-BD and invasive cancers is still lacking. OBJECTIVES: This study aims to investigate the underlying molecular mechanisms of this malignant progression in the skin and internal organs. METHODS: This is a biopsy-based follow-up study. We tested the DNA histograms, Cyclin D1 (CCND1) protein expression and CCND1 promoter DNA methylation in 40 pathologically confirmed specimens from As-BD patients to correlate with individual's invasive cancer occurrence in the 5-year follow-up. RESULTS: Flow cytometric DNA histogram analysis of skin specimens showed aneuploid (n=15), G2/M arrest (n=22), and normal (n=3) DNA histograms. No patients with normal DNA histograms developed invasive cancers, whereas 13 developed invasive cancers in the aneuploid group and 2 developed invasive cancers in the G2/M arrest group. The aneuploid group showed a high risk of invasive cancer development. In all assessed aneuploid specimens, the CCND1 promoter hypomethylation was observed. Statistically, percentage of un-methylation more than 55.85% among 17 detected CpG sites showed extremely high predictive power in the occurrence of invasive arsenical cancers. Furthermore, the un-methylation at -56 and -54bp CpG sites was statistically significantly associated with invasive arsenical cancer development (p=1.29x10(-5)). CONCLUSIONS: As-BD lesions showing an aneuploid DNA histogram had a high risk of invasive cancer development. Un-methyaltion at -56 and -54bp CpG in the CCND1 promoter serves as a predictor for invasive progression in As-BD patients.
    日期: 2018-02
    關聯: Journal of Dermatological Science. 2018 Feb;89(2):191-197.
    Link to: http://dx.doi.org/10.1016/j.jdermsci.2017.10.003
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0923-1811&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000425580500011
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85035069419
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