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Methylation profile of TP53 regulatory pathway and mtDNA alterations in breast cancer patients lacking TP53 mutations

Barekati, Zeinab and Radpour, Ramin and Kohler, Corina and Zhang, Bei and Toniolo, Paolo and Lenner, Per and Lv, Qing and Zheng, Hong and Zhong, Xiao Yan. (2010) Methylation profile of TP53 regulatory pathway and mtDNA alterations in breast cancer patients lacking TP53 mutations. Human molecular genetics, Vol. 19, H. 15. pp. 2936-2946.

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Official URL: http://edoc.unibas.ch/dok/A6004427

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Abstract

The present study investigated promoter hypermethylation of TP53 regulatory pathways providing a potential link between epigenetic changes and mitochondrial DNA (mtDNA) alterations in breast cancer patients lacking a TP53 mutation. The possibility of using the cancer-specific alterations in serum samples as a blood-based test was also explored. Triple-matched samples (cancerous tissues, matched adjacent normal tissues and serum samples) from breast cancer patients were screened for TP53 mutations, and the promoter methylation profile of P14(ARF), MDM2, TP53 and PTEN genes was analyzed as well as mtDNA alterations, including D-loop mutations and mtDNA content. In the studied cohort, no mutation was found in TP53 (DNA-binding domain). Comparison of P14(ARF) and PTEN methylation patterns showed significant hypermethylation levels in tumor tissues (P > 0.05 and >0.01, respectively) whereas the TP53 tumor suppressor gene was not hypermethylated (P > 0.511). The proportion of PTEN methylation was significantly higher in serum than in the normal tissues and it has a significant correlation to tumor tissues (P > 0.05). mtDNA analysis revealed 36.36% somatic and 90.91% germline mutations in the D-loop region and also significant mtDNA depletion in tumor tissues (P > 0.01). In addition, the mtDNA content in matched serum was significantly lower than in the normal tissues (P > 0.05). These data can provide an insight into the management of a therapeutic approach based on the reversal of epigenetic silencing of the crucial genes involved in regulatory pathways of the tumor suppressor TP53. Additionally, release of significant aberrant methylated PTEN in matched serum samples might represent a promising biomarker for breast cancer.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Gynecological Oncology (Zhong)
UniBasel Contributors:Zhong, Xiao Yan
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Oxford Univ. Press
ISSN:0964-6906
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:19 Jul 2013 07:43
Deposited On:19 Jul 2013 07:35

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