CYP1A1 contiguous hypermethylation within a putative CpG block is associated with breast cancer progression: Feasibility to define boundary motives

Hossein Dehdari; Fatemeh Moradian; Ali Barzegar; Mohammad Ali Ebrahimzadeh

doi:10.1016/j.yexcr.2022.113062

CYP1A1 contiguous hypermethylation within a putative CpG block is associated with breast cancer progression: Feasibility to define boundary motives

Exp Cell Res. 2022 Apr 1;413(1):113062. doi: 10.1016/j.yexcr.2022.113062. Epub 2022 Feb 12.

Authors

Hossein Dehdari¹, Fatemeh Moradian¹, Ali Barzegar², Mohammad Ali Ebrahimzadeh³

Affiliations

¹ Department of Basic Sciences, Sari Agricultural Sciences and Natural Resources University, Sari, Iran.
² Department of Basic Sciences, Sari Agricultural Sciences and Natural Resources University, Sari, Iran. Electronic address: alibar647@yahoo.com.
³ Department of Medicinal Chemistry, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

PMID: 35167827
DOI: 10.1016/j.yexcr.2022.113062

Abstract

Having broad specificity for xenobiotics metabolism throughout the body, cytochrome P450 (CYP) isoform 1A1 is of key relevance for carcinogenesis. However, the oncogenic potential of its altered transcription and the underlying mechanism has not been well-established in breast cancer. Direct bisulfite sequencing PCR (BSP) of the CYP1A1 promoter, enriched by 113 CpGs within and flanking the xenobiotic response elements (XREs) 2 to 10, in paired cancerous and normal tissues from 40 breast cancer patients revealed three distinctly methylated patterns; unmethylated (XREs 2 to 6) and completely methylated (XREs 7 and 8) CpGs, in common for the normal and cancerous tissues, and a putative 171bp CpG block (XREs 9 and 10) contiguously hypermethylated in the tumor tissues. Increased transcription of CYP1A1, observed for the cancerous tissues, was correlated with the hypermethylation of given CpG block, besides simultaneously being associated with upregulation of the anti-apoptotic BCL-2. Clinical value of the methylation changes, investigated based on the comparisons between the tissue cohorts of different clinicopathological features, exhibited gradual hypermethylation of the corresponding CpG block following disease progression as well as lymphatic involvement. Hypermethylation of given CpG block may has potential to be used as a biomarker for diagnosis and progression of breast cancer.

Keywords: Bisulfite sequencing PCR (BSP); Breast cancer; CYP1A1; CpG; DNA Methylation.