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Correlation of telomere length shortening with promoter methylation profile of p16/Rb and p53/p21 pathways in breast cancer

Radpour, Ramin and Barekati, Zeinab and Haghighi, Mahdi Montazer and Kohler, Corina and Asadollahi, Reza and Torbati, Peyman Mohammadi and Holzgreve, Wolfgang and Zhong, Xiao Yan. (2010) Correlation of telomere length shortening with promoter methylation profile of p16/Rb and p53/p21 pathways in breast cancer. Modern pathology, Vol. 23, no. 5. pp. 763-772.

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Official URL: http://edoc.unibas.ch/dok/A6003033

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Abstract

Unregulated cell growth, a major hallmark of cancer, is coupled with telomere shortening. Measurement of telomere length could provide important information on cell replication and proliferation state in cancer tissues. Telomere shortening and its potential correlation with downregulation of cell-cycle regulatory elements were studied by the examination of relative telomere length and methylation status of the TP53, P21 and P16 promoters in tissues from breast cancer patients. Telomere length was measured in 104 samples (52 tumors and paired adjacent normal breast tissues) by quantitative PCR. Methylation profile of selected genes was analyzed in all samples using a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Our results demonstrated a significant shortening of tumor telomere regions compared with paired adjacent normal tissues (P>0.001). Similarly, telomere lengths were significantly shorter in advanced stage cases and in those with higher histological grades (P>0.05). Telomere shortening in cancer tissues was correlated with a different level of hypermethylation in the TP53, P21 and P16 promoters (r=-0.33, P=0.001; r=-0.70, P>0.0001 and r=-0.71, P>0.0001, respectively). The results suggested that inactivation of p16/Rb and/or p53/p21 pathways by hypermethylation may be linked to critical telomere shortening, leading to genome instability and ultimately to malignant transformation. Thus, telomere shortening and promoter hypermethylation of related genes both might serve as breast cancer biomarkers.
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:Nature Publishing Group
ISSN:0893-3952
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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