Detection of aberrant methylation of a six-gene panel in serum DNA for diagnosis of breast cancer

// Ming Shan 1, 2, * , Huizi Yin 1, * , Junnan Li 3 , Xiaobo Li 4 , Dong Wang 5 , Yonghui Su 1 , Ming Niu 1 , Zhenbin Zhong 1 , Ji Wang 1 , Xianyu Zhang 1 , Wenli Kang 6 , Da Pang 1, 2 1 Department of Breast Cancer Surgery, the Affiliated Tumor Hospital of Harbin Medical University, Harbin, P.R. China 2 Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, P.R. China 3 Department of Epidemiology and Biostatistics, Harbin Medical University, Harbin, P.R. China 4 Department of Pathology, Harbin Medical University, Harbin, P.R. China 5 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P.R. China 6 Department of Oncology, General Hospital of Heilongjiang Province Land Reclamation Headquarters, Harbin, P.R. China * These authors have contributed equally to this work Correspondence to: Da Pang, e-mail: pangda@ems.hrbmu.edu.cn Keywords: breast cancer, DNA methylation, diagnosis, MethyLight Received: December 08, 2015     Accepted: February 11, 2016     Published: February 23, 2016 ABSTRACT Detection of breast cancer at an early stage is the key for successful treatment and improvement of outcome. However the limitations of mammography are well recognized, especially for those women with premenopausal breast cancer. Novel approaches to breast cancer screening are necessary, especially in the developing world where mammography is not feasible. In this study, we examined the promoter methylation of six genes (SFN, P16, hMLH1, HOXD13, PCDHGB7 and RASSF1a) in circulating free DNA (cfDNA) extracted from serum. We used a high-throughput DNA methylation assay (MethyLight) to examine serum from 749 cases including breast cancer patients, patients with benign breast diseases and healthy women. The six-gene methylation panel test achieved 79.6% and 82.4% sensitivity with a specificity of 72.4% and 78.1% in diagnosis of breast cancer when compared with healthy and benign disease controls, respectively. Moreover, the methylation panel positive group showed significant differences in the following independent variables: ( a ) involvement of family history of tumors; ( b ) a low proliferative index, ki-67; ( c ) high ratios in luminal subtypes. Additionally the panel also complemented some breast cancer cases which were neglected by mammography or ultrasound. These data suggest that epigenetic markers in serum have potential for diagnosis of breast cancer.