Title
Quantitative methylation profiling in tumor and matched morphologically normal tissues from breast cancer patients
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
London ,
Subject
Human medicine
Source (journal)
BMC cancer. - London
Volume/pages
10(2010) , p. 97,1-97,8
ISSN
1471-2407
ISI
000276329100002
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Background In the present study, we determined the gene hypermethylation profiles of normal tissues adjacent to invasive breast carcinomas and investigated whether these are associated with the gene hypermethylation profiles of the corresponding primary breast tumors. Methods A quantitative methylation-specific PCR assay was used to analyze the DNA methylation status of 6 genes (DAPK, TWIST, HIN-1, RASSF1A, RARβ2 and APC) in 9 normal breast tissue samples from unaffected women and in 56 paired cancerous and normal tissue samples from breast cancer patients. Results Normal tissue adjacent to breast cancer displayed statistically significant differences to unrelated normal breast tissues regarding the aberrant methylation of the RASSF1A (P = 0.03), RARβ2 (P = 0.04) and APC (P = 0.04) genes. Although methylation ratios for all genes in normal tissues from cancer patients were significantly lower than in the cancerous tissue from the same patient (P ≤ 0.01), in general, a clear correlation was observed between methylation ratios measured in both tissue types for all genes tested (P < 0.01). When analyzed as a categorical variable, there was a significant concordance between methylation changes in normal tissues and in the corresponding tumor for all genes tested but RASSF1A. Notably, in 73% of patients, at least one gene with an identical methylation change in cancerous and normal breast tissues was observed. Conclusions Histologically normal breast tissues adjacent to breast tumors frequently exhibit methylation changes in multiple genes. These methylation changes may play a role in the earliest stages of the development of breast neoplasia.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/d56769/17d55b64.pdf
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