Cyclin D1 promoter -56 and -54bp CpG un-methylation predicts invasive progression in arsenic-induced Bowen's disease.
J Dermatol Sci
; 89(2): 191-197, 2018 Feb.
Article
en En
| MEDLINE
| ID: mdl-29103775
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 -54bp CpG in the CCND1 promoter serves as a predictor for invasive progression in As-BD patients.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Arsénico
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Neoplasias Cutáneas
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Enfermedad de Bowen
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Regiones Promotoras Genéticas
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Ciclina D1
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Dermatol Sci
Asunto de la revista:
DERMATOLOGIA
Año:
2018
Tipo del documento:
Article