title: Methylation of the SEPT9_v2 promoter as a novel marker for the detection of circulating tumor DNA in breast cancer patients.
abstract: The aim of the present study was to evaluate the promoter methylation status of SEPT9_v2 in breast cancer and to detect this methylated gene in circulating tumor DNA (ctDNA) in plasma. Bisulfite sequencing was performed with a next generation sequencer. Methylation of the SEPT9_v2 promoter was found in 67% (8/12) of breast cancer cell lines and 53% (10/19) of breast tumor tissue, but not in normal breast tissue (0/19). A clear inverse correlation was observed between the expression of SEPT9_v2 mRNA and the methylation index (MI) both in cell lines and breast cancer tissues. The MI of SEPT9_v2 was significantly higher in non-basal subtype of breast cancer (13.0%, n=84) than in basal subtype (3.0%, n=23) (P<0.0001). Methylated SEPT9_v2 ctDNA in plasma was detected in 11% (9/82) of primary breast cancer patients and 52% (26/50) of metastatic breast cancer patients, but not in the healthy controls (0/51). These results indicate that SEPT9_v2 promoter hypermethylation, which silences the expression of SEPT9_v2 mRNA, is observed in a significant proportion of breast tumors, and that methylated SEPT9_v2 may serve as a novel tumor marker for breast cancer.
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors: Saki
authors: S
authors: Matsui
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors: Naofumi
authors: N
authors: Kagara
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors: Chieko
authors: C
authors: Mishima
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors: Yasuto
authors: Y
authors: Naoi
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors: Masafumi
authors: M
authors: Shimoda
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors: Atsushi
authors: A
authors: Shimomura
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors: Kenzo
authors: K
authors: Shimazu
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors: Seung Jin
authors: SJ
authors: Kim
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors: Shinzaburo
authors: S
authors: Noguchi
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D011401:Promoter Regions, Genetic; D058112:Septins / Q000097:blood / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C474315:SEPTIN9 protein, human; D058112:Septins