Assessment of DAPK1 and CAVIN3 Gene Promoter Methylation in Breast Invasive Ductal Carcinoma and Metastasis

Document Type : Original Article


1 .Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 .Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

3 .Department of Surgery, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran

4 4.Iran National Tumor Bank, Cancer Institute of Iran, Tehran, University of Medical Sciences, Tehran, Iran


Metastasis might be latent or occur several years after primary tumor removal. Currently used methods for detection of distant metastasis have still some limitations. Blood tests may improve sensitivity and specificity of currently used screening procedures. The present study was designed to investigate promoter methylation status of DAPK1 and CAVIN3 genes in plasma circulating free DNA (cfDNA) samples in Iranian invasive ductal carcinoma (IDC) patients. We also investigated association of two gene promoter methylations with breast cancer (BC) and metastatic BC was also assessed.
Materials and Methods
In this case-control study, MethySYBR assay was performed to determine DAPK1 and CAVIN3 promoter methylation status in breast IDC from 90 patients and 30 controls. Based on clinicopathological information, patient samples subdivided into stage I, II/III and IV groups (each group contained 30 individuals).
According to the results an increased promoter methylation level of the DAPK1 gene in BC patients was observed. It was found that as disease progressed, the percentage of methylation was changed while it was not significant. Methylation changes in metastatic and non-metastatic BC revealed that methylation levels were significantly increased in metastatic than non-metastatic group. Analysis revealed that promoter methylation of CAVIN3 gene in BC patients was significantly increased. The observed methylation changes from less to more invasive stages were not significant in the CAVIN3 gene. Moreover, promoter methylation was changed in metastatic rather than non-metastatic condition, although it was not significant.
Promoter hypermethylation of DAPK1 and CAVIN3 genes in plasma are associated with the risk of BC and they can be potential diagnostic biomarkers along with current methods. Additionally, association of aberrant DAPK1 promoter methylation with metastasis suggests its potential usage as a non-invasive strategy for metastatic BC diagnosis.