Open AccessPrognostic Relevance of Promoter Hypermethylation of Multiple Genes in Breast Cancer Patients
Author(s) -
Gayatri Sharma,
Sameer Mirza,
Yoona Yang,
Rajinder Parshad,
Priya Hazrah,
Sanchita Gupta,
Ranju Ralhan
Publication year - 2009
Publication title -
analytical cellular pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.576
H-Index - 24
eISSN - 2210-7185
pISSN - 2210-7177
DOI - 10.1155/2009/416923
Subject(s) - methylation , gstp1 , dna methylation , breast cancer , cancer research , gene silencing , gene , biology , promoter , oncology , tumor suppressor gene , cancer , carcinogenesis , medicine , genetics , genotype , gene expression
Background : Methylation-mediated suppression of detoxification, DNA repair and tumor suppressor genes has been implicated in cancer development. This study was designed to investigate the impact of concurrent methylation of multiple genes in breast tumors on disease prognosis. Methods : Methylation specific PCR was carried out to analyze the methylation status of seven genes in archived breast tissues and determine the effect of aberrant methylation of multiple genes on disease prognosis and patients’ survival. Results : Promoter hypermethylation was observed in PRB 67%, ER α 64%, RASSF1A 63%, p16INK4A 51%, PRBβ 2 22%, GSTP1 25% and BRCA1 27% of the breast cancers, respectively. Concurrent methylation of BRCA1, ER α , GSTP1 and RAR β 2, was observed in a large proportion of breast cancers analyzed, suggesting that these genes do not appear to be methylated alone. Patients with high methylation indices had poor prognosis ( p < 0.001, Hazards ratio = 14.58). Cox regression analysis showed RAR β 2 promoter methylation to be an independent important determinant of breast cancer prognosis. Conclusions : Our results suggest that methylation of multiple genes plays an important role in prognosis of breast cancer. Our study not only describes the association of methylation mediated silencing of multiple genes with the severity of disease, but also drives to speculate the molecular crosstalk between genes or genetic pathways regulated by them individually.