Titre
Methylation profile of TP53 regulatory pathway and mtDNA alterations in breast cancer patients lacking TP53 mutations.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Barekati, Zeinab
Auteure/Auteur
Radpour, Ramin
Auteure/Auteur
Kohler, Corina
Auteure/Auteur
Zhang, Bei
Auteure/Auteur
Toniolo, Paolo
Auteure/Auteur
Lenner, Per
Auteure/Auteur
Lv, Qing
Auteure/Auteur
Zheng, Hong
Auteure/Auteur
Zhong Xiao, Yan
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1460-2083[electronic], 0964-6906[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
19
Numéro
15
Première page
2936
Dernière page/numéro d’article
2946
Peer-reviewed
Oui
Langue
anglais
Résumé
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.
Sujets
PID Serval
serval:BIB_085EA78EAF45
PMID
Open Access
Oui
Date de création
2010-12-23T15:59:14.953Z
Date de création dans IRIS
2025-05-20T17:12:15Z
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Nom
BIB_085EA78EAF45.P001.pdf
Version du manuscrit
preprint
Taille
523.68 KB
Format
Adobe PDF
PID Serval
serval:BIB_085EA78EAF45.P001
URN
urn:nbn:ch:serval-BIB_085EA78EAF452
Somme de contrôle
(MD5):26b92ce93c4f7c27d72bd5460493c982