Aberrant promoter hypermethylation and genomic hypomethylation in tumor, adjacent normal tissues and blood from breast cancer patients.
BACKGROUND
Promoter hypermethylation and global hypomethylation in the human genome are hallmarks of most cancers. Detection of aberrant methylation in white blood cells (WBC) has been suggested as a marker for cancer development, but has not been extensively investigated. This study was carried out to determine whether aberrant methylation in WBC DNA can be used as a surrogate biomarker for breast cancer risk.


METHODS
Promoter hypermethylation of 8 tumor suppressor genes (RASSF1A, APC, HIN1, BRCA1, CYCLIND2, RARbeta, CDH1 and TWIST1) and DNA methylation for three repetitive elements (LINE1, Sat2 and Alu) were analyzed in invasive ductal carcinoma of the breast, paired adjacent normal tissue and WBC from 40 breast cancer patients by the MethyLight assay. Methylation in WBC from 40 controls was also analyzed.


RESULTS
Tumor and adjacent tissues showed frequent hypermethylation for all genes tested, while WBC DNA was rarely hypermethylated. For HIN1, RASSF1A, APC and TWIST1, there was agreement between hypermethylation in tumor and adjacent tissues (p=0.04, p=0.02, p=0.005 and p<0.0001, respectively). DNA methylation for the three repetitive elements was lower in tumor compared to adjacent tissue and WBC DNA. Significant correlations in the methylation of Sat2M1 between tumor and adjacent tissues and WBC DNA were found (p<0.0001 and p=0.046, respectively). There was also a significant difference in methylation of Sat2M1 between cases and controls (p=0.01).


CONCLUSIONS
These results suggest that further studies of WBC methylation, including prospective studies, may provide biomarkers of breast cancer risk.
Cho
Yoon Hee
YH
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 630 West 168 St. New York, NY 10032, USA.
Yazici
Hulya
H
Wu
Hui-Chen
HC
Terry
Mary Beth
MB
Gonzalez
Karina
K
Qu
Mengxue
M
Dalay
Nejat
N
Santella
Regina M
RM
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000737:chemistry / Q000502:physiology; D008875:Middle Aged; D011401:Promoter Regions, Genetic
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm