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.