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%, ERalpha 64%, RASSF1A 63%, p16INK4A 51%, RARbeta2 22%, GSTP1 25% and BRCA1 27% of the breast cancers, respectively. Concurrent methylation of BRCA1, ERalpha, GSTP1 and RARbeta2, 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 RARbeta2 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.
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%, ERalpha 64%, RASSF1A 63%, p16INK4A 51%, RARbeta2 22%, GSTP1 25% and BRCA1 27% of the breast cancers, respectively. Concurrent methylation of BRCA1, ERalpha, GSTP1 and RARbeta2, 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 RARbeta2 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.
Authors: Yoon Hee Cho; Jing Shen; Marilie D Gammon; Yu-Jing Zhang; Qiao Wang; Karina Gonzalez; Xinran Xu; Patrick T Bradshaw; Susan L Teitelbaum; Gail Garbowski; Hanina Hibshoosh; Alfred I Neugut; Jia Chen; Regina M Santella Journal: Breast Cancer Res Treat Date: 2011-08-12 Impact factor: 4.872
Authors: C Matuschek; Edwin Bölke; G Lammering; P A Gerber; M Peiper; W Budach; H Taskin; H B Prisack; G Schieren; K Orth; H Bojar Journal: Eur J Med Res Date: 2010 Impact factor: 2.175
Authors: Robert Kornegoor; Cathy B Moelans; Anoek Hj Verschuur-Maes; Marieke Ch Hogenes; Peter C de Bruin; Joost J Oudejans; Paul J van Diest Journal: Breast Cancer Res Date: 2012-07-05 Impact factor: 6.466
Authors: Shahab Akhoondi; Linda Lindström; Martin Widschwendter; Martin Corcoran; Jonas Bergh; Charles Spruck; Dan Grandér; Olle Sangfelt Journal: Breast Cancer Res Date: 2010-12-01 Impact factor: 6.466