Cyclin D1 promoter -56 and -54bp CpG un-methylation predicts invasive progression in arsenic-induced Bowen's disease

Wei Ting Liao, Huey Ling You, Chee Yin Chai, Chih Hung Lee, Cheng Che E. Lan, Shun Jen Chang, Chu Ling Yu, Hsin Su Yu

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    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=1.29×10-5). Conclusions: As-BD lesions showing an aneuploid DNA histogram had a high risk of invasive cancer development. Un-methyaltion at -56 and -54. bp CpG in the CCND1 promoter serves as a predictor for invasive progression in As-BD patients.

    Original languageEnglish
    JournalJournal of Dermatological Science
    DOIs
    Publication statusAccepted/In press - Jan 1 2017

    Fingerprint

    Bowen's Disease
    Methylation
    Cyclin D1
    Arsenic
    Aneuploidy
    DNA
    Arsenicals
    Skin
    Neoplasms
    Biopsy
    Association reactions
    Skin Neoplasms
    DNA Methylation
    Urinary Bladder
    Proteins
    Lung

    Keywords

    • Aneuploidy
    • Arsenic-induced Bowen's disease
    • Cyclin D1 un-methylation
    • Invasive progression
    • Predictor

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Dermatology

    Cite this

    Cyclin D1 promoter -56 and -54bp CpG un-methylation predicts invasive progression in arsenic-induced Bowen's disease. / Liao, Wei Ting; You, Huey Ling; Chai, Chee Yin; Lee, Chih Hung; Lan, Cheng Che E.; Chang, Shun Jen; Yu, Chu Ling; Yu, Hsin Su.

    In: Journal of Dermatological Science, 01.01.2017.

    Research output: Contribution to journalArticle

    Liao, Wei Ting ; You, Huey Ling ; Chai, Chee Yin ; Lee, Chih Hung ; Lan, Cheng Che E. ; Chang, Shun Jen ; Yu, Chu Ling ; Yu, Hsin Su. / Cyclin D1 promoter -56 and -54bp CpG un-methylation predicts invasive progression in arsenic-induced Bowen's disease. In: Journal of Dermatological Science. 2017.
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    title = "Cyclin D1 promoter -56 and -54bp CpG un-methylation predicts invasive progression in arsenic-induced Bowen's disease",
    abstract = "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=1.29×10-5). Conclusions: As-BD lesions showing an aneuploid DNA histogram had a high risk of invasive cancer development. Un-methyaltion at -56 and -54. bp CpG in the CCND1 promoter serves as a predictor for invasive progression in As-BD patients.",
    keywords = "Aneuploidy, Arsenic-induced Bowen's disease, Cyclin D1 un-methylation, Invasive progression, Predictor",
    author = "Liao, {Wei Ting} and You, {Huey Ling} and Chai, {Chee Yin} and Lee, {Chih Hung} and Lan, {Cheng Che E.} and Chang, {Shun Jen} and Yu, {Chu Ling} and Yu, {Hsin Su}",
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    TY - JOUR

    T1 - Cyclin D1 promoter -56 and -54bp CpG un-methylation predicts invasive progression in arsenic-induced Bowen's disease

    AU - Liao, Wei Ting

    AU - You, Huey Ling

    AU - Chai, Chee Yin

    AU - Lee, Chih Hung

    AU - Lan, Cheng Che E.

    AU - Chang, Shun Jen

    AU - Yu, Chu Ling

    AU - Yu, Hsin Su

    PY - 2017/1/1

    Y1 - 2017/1/1

    N2 - 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=1.29×10-5). Conclusions: As-BD lesions showing an aneuploid DNA histogram had a high risk of invasive cancer development. Un-methyaltion at -56 and -54. bp CpG in the CCND1 promoter serves as a predictor for invasive progression in As-BD patients.

    AB - 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=1.29×10-5). Conclusions: As-BD lesions showing an aneuploid DNA histogram had a high risk of invasive cancer development. Un-methyaltion at -56 and -54. bp CpG in the CCND1 promoter serves as a predictor for invasive progression in As-BD patients.

    KW - Aneuploidy

    KW - Arsenic-induced Bowen's disease

    KW - Cyclin D1 un-methylation

    KW - Invasive progression

    KW - Predictor

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    U2 - 10.1016/j.jdermsci.2017.10.003

    DO - 10.1016/j.jdermsci.2017.10.003

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    JF - Journal of Dermatological Science

    SN - 0923-1811

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