RASSF1A and CDH1 hypermethylation as potential epimarkers in breast cancer.
Breast cancer is the most common cancer in women worldwide, representing 28.2% of all female malignancies. In addition to genetic changes, epigenetic events, as aberrant DNA methylation and histone modification, are responsible for cancer development. Many tumour suppressor genes are inactivated by DNA hypermethylation, which could be utilized for identification of new epigenetic biomarkers. To investigate the relation between DNA methylation level and breast cancer progression, we analysed DNA methylation in RASSF1A and CDH1 promoters using quantitative multiplex methylation-specific PCR in paraffin-embedded tumour tissues and blood samples from 92 breast cancer patients and 50 controls, respectively. The associations between RASSF1A and CDH1 methylation levels and clinico-pathological parameters were tested by Kruskal-Wallis and van der Waerden ANOVA tests. Out of 92 breast cancer patients, 76 (82.6%) manifested various levels of RASSF1A (range from 1.20 to 92.63%) and 20 (21.7%) of CDH1 (range from 1.20 to 79.62%) methylation. However, no methylation was found in 50 controls. Increasing trends in RASSF1A methylation were observed in tumour size, lymph node status and TNM stage, but only CDH1 methylation levels showed statistically significant differences between the patient subgroups in lymph node status and IHC subtype. Overall, stable relatively high RASSF1A methylation could be utilised as universal tumour marker and the less frequent but highly methylated CDH1 promoter can serve for identification of potentially metastasising tumours.
Laboratory of Cancer Genetics, Cancer Research Institute of the Slovak Academy of Sciences, Bratislava, Slovakia.
Katarina
K
Sebova
Iveta
I
Zmetakova
Vladimir
V
Bella
Karol
K
Kajo
Iveta
I
Stankovicova
Viera
V
Kajabova
Tomas
T
Krivulcik
Zora
Z
Lasabova
Miroslav
M
Tomka
Stefan
S
Galbavy
Ivana
I
Fridrichova
D000368:Aged; D000704:Analysis of Variance; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015820:Cadherins / Q000235:genetics*; D002138:Calibration; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019175:DNA Methylation; D055088:Early Detection of Cancer / Q000379:methods; D044127:Epigenesis, Genetic; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction / Q000592:standards; D012015:Reference Standards; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins