Frequent Promoter Methylation of CDH1, DAPK, RARB, and HIC1 Genes in Carcinoma of Cervix Uteri: Its Relationship to Clinical OutcomeReport as inadecuate




Frequent Promoter Methylation of CDH1, DAPK, RARB, and HIC1 Genes in Carcinoma of Cervix Uteri: Its Relationship to Clinical Outcome - Download this document for free, or read online. Document in PDF available to download.

Molecular Cancer

, 2:24

First Online: 13 May 2003Received: 05 May 2003Accepted: 13 May 2003

Abstract

BackgroundCervical cancer CC, a leading cause of cancer-related deaths in women worldwide, has been causally linked to genital human papillomavirus HPV infection. Although a host of genetic alterations have been identified, molecular basis of CC development is still poorly understood.

ResultsWe examined the role of promoter hypermethylation, an epigenetic alteration that is associated with the silencing tumor suppressor genes in human cancer, by studying 16 gene promoters in 90 CC cases. We found a high frequency of promoter methylation in CDH1, DAPK, RARB, and HIC1 genes. Correlation of promoter methylation with clinical characteristics and other genetic changes revealed the following: a overall promoter methylation was higher in more advanced stage of the disease, b promoter methylation of RARB and BRCA1 predicted worse prognosis, and c the HIC1 promoter methylation was frequently seen in association with microsatellite instability. Promoter methylation was associated with gene silencing in CC cell lines. Treatment with methylation or histone deacetylation-inhibiting agents resulted in profound reactivation of gene expression.

ConclusionsThese results may have implications in understanding the underlying epigenetic mechanisms in CC development, provide prognostic indicators, and identify important gene targets for treatment.

Keywordscervical carcinoma promoter hypermethylation CDH1 DAP K RARB tumor suppressor gene gene expression Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-2-24 contains supplementary material, which is available to authorized users.

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Author: Gopeshwar Narayan - Hugo Arias-Pulido - Sanjay Koul - Hernan Vargas - Fang F Zhang - Jeannine Villella - Achim Schneider -

Source: https://link.springer.com/



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