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01-02-2020 | Breast Cancer | Epidemiology

The novel TP53 3′-end methylation pattern associated with its expression would be a potential biomarker for breast cancer detection

Authors: Feng Zeng, Jianfu Heng, Xinwu Guo, Yue Wang, Wenhan Wu, Lili Tang, Min Chen, Shouman Wang, Hongyu Deng, Jun Wang

Published in: Breast Cancer Research and Treatment | Issue 1/2020

Abstract

Background

Deficiency or silence of TP53 is an early event in breast tumorigenesis. Aberrant methylation and mutation in regulatory regions were considered as crucial regulators of gene expression.

Methods

Using multiplex-PCR and next-generation sequencing technology, we analyzed TP53 mutation spectrum in its promoter region. Using PCR target sequence enrichment and next-generation bisulfite sequencing technology, we analyzed the methylation profile of the promoter and 3′-end regions of TP53 gene in paired breast tumor and normal tissues from 120 breast cancer patients. The expression of TP53 and the flanking gene ATP1B2 was explored with qPCR method in the same cohort.

Results

No promoter mutation of TP53 gene was found in the cohort of the 120 breast cancer patients. The 3′-end of TP53 gene was hyper-methylated (average 78.71%) compared with the promoter region (average less than 1%) in breast tumor tissues. TP53 was significantly lower expressed (P = 1.68E−15) and hyper-methylated in 3′-end (P = 1.82E−18) in tumor. Negative cis correlation was found between the TP53 expression and its 3′-end methylation (P = 9.02E−8, R = 0.337). TP53 expression was significantly associated with PR status (P = 0.0128), Ki67 level (P = 0.0091), and breast cancer subtypes (P = 0.0109). TP53 3′-end methylation and expression showed a good performance in discriminating breast cancer and normal tissues with an AUC of 0.930.

Conclusions

The 3′-end methylation of TP53 might be a crucial regulator for its expression in breast cancer, suggesting that TP53 3′-end hyper-methylation associated with its lower expression could be a potential biomarker for breast cancer diagnosis.

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Title: The novel TP53 3′-end methylation pattern associated with its expression would be a potential biomarker for breast cancer detection
Authors: Feng Zeng
Jianfu Heng
Xinwu Guo
Yue Wang
Wenhan Wu
Lili Tang
Min Chen
Shouman Wang
Hongyu Deng
Jun Wang
Publication date: 01-02-2020
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Biomarkers
Published in: Breast Cancer Research and Treatment / Issue 1/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05536-2

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