TY - JOUR
T1 - Prognostic relevance of promoter hypermethylation of multiple genes in breast cancer patients
AU - Sharma, Gayatri
AU - Mirza, Sameer
AU - Yang, Yi Hsin
AU - Parshad, Rajinder
AU - Hazrah, Priya
AU - Datta Gupta, Siddartha
AU - Ralhan, Ranju
PY - 2009
Y1 - 2009
N2 - 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%, ERα 64%, RASSF1A 63%, p16INK4A 51%, RARβ2 22%, GSTP1 25% and BRCA1 27% of the breast cancers, respectively. Concurrent methylation of BRCA1, ERα, GSTP1 and RARβ2, 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 RARβ2 promoter methylation to be an independent important determinant of breast cancer prognosis. Conclusion: 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.
AB - 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%, ERα 64%, RASSF1A 63%, p16INK4A 51%, RARβ2 22%, GSTP1 25% and BRCA1 27% of the breast cancers, respectively. Concurrent methylation of BRCA1, ERα, GSTP1 and RARβ2, 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 RARβ2 promoter methylation to be an independent important determinant of breast cancer prognosis. Conclusion: 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.
KW - BRCA1
KW - Breast cancer
KW - GSTP1
KW - Methylation
KW - Prognosis
KW - RARβ
UR - http://www.scopus.com/inward/record.url?scp=71949122380&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71949122380&partnerID=8YFLogxK
U2 - 10.3233/CLO-2009-0507
DO - 10.3233/CLO-2009-0507
M3 - Article
C2 - 19940364
AN - SCOPUS:71949122380
SN - 1570-5870
VL - 31
SP - 487
EP - 500
JO - Cellular Oncology
JF - Cellular Oncology
IS - 6
ER -