title: Promoter methylation of TRIM9 as a marker for detection of circulating tumor DNA in breast cancer patients.
abstract: The aim of the present study was to investigate the promoter methylation status of TRIM9 in breast cancer and to determine the presence of TRIM9-methylated circulating tumor DNA (ctDNA) in plasma. Bisulfite sequencing with a next generation sequencer showed TRIM9 promoter methylation in 92 % (11/12) of breast cancer cell lines (BCCs) and 68 % (13/19) of breast tumor tissues but not in any normal breast tissues (0/19). Methylation ratio of TRIM9 was significantly lower in basal type (9 %, n = 23) than luminal A (69 %, n = 29, P = 0.0003). Quantitative RT-PCR of BCCs disclosed an inverse correlation between TRIM9 mRNA expression and methylation ratio. TRIM9 methylated ctDNA in plasma was detected in 18 % (10/56) of metastatic breast cancer patients but not in any of 60 healthy controls. These results indicate that TRIM9 promoter hypermethylation, which suppresses TRIM9 mRNA expression, occurs in a significant proportion of breast tumors, and that TRIM9-methylated ctDNA thus may serve as a tumor marker for breast cancer.
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Mishima
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Kagara
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Matsui
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Tanei
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Naoi
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimomura
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Shimazu
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
keywords: Biomarker; Breast cancer; Methylation; TRIM9