BACKGROUND: Circulating @entity5 cells (CTCs) are associated with prognosis in a variety of @entity1 @entity5 and have been proposed as a liquid biopsy for follow-up examinations. We show that @entity5 suppressor and @entity3 suppressor genes are epigenetically silenced in CTCs isolated from peripheral blood of @entity0 @entity1 . METHODS: We obtained peripheral blood from 56 @entity1 with operable @entity0 , 27 @entity1 with verified @entity3 , and 23 healthy individuals. We tested DNA extracted from the EpCAM-positive immunomagnetically selected CTC fraction for the presence of methylated and unmethylated @entity57911 , @entity13311 , and @entity13050 promoter sequences by methylation-specific PCR (MSP). All samples were checked for @entity4166 ( @entity4166 , formerly @entity4166 ) expression by reverse-transcription quantitative PCR. RESULTS: In CTCs of @entity1 with operable @entity0 , promoter methylation of @entity57911 was observed in 17.9%, @entity13311 in 32.1%, and @entity13050 in 53.6% of @entity1 . In CTCs of @entity1 with verified @entity3 , promoter methylation of @entity57911 was observed in 37.0%, @entity13311 in 44.4%, and @entity13050 in 74.1%. In healthy individuals, promoter methylation of @entity57911 was observed in 4.3%, @entity13311 in 8.7%, and @entity13050 in 4.3%. DNA methylation of these genes for both operable and metastatic @entity0 was significantly different from that of the control population. CONCLUSIONS: DNA methylation of @entity5 suppressor and @entity3 suppressor genes is a hallmark of CTCs and confirms their heterogeneity. Our findings add a new dimension to the molecular characterization of CTCs and may underlie the acquisition of malignant properties, including their stem-like phenotype.

DNA methylation of XXXX suppressor and @entity3 suppressor genes in circulating @entity5 cells.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity4166 :: ('3880', 'Gene') :: ['keratin 19', 'CK-19', 'KRT19'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancers'] @entity13050 :: ('64321', 'Gene') :: ['SOX17'] @entity13311 :: ('25855', 'Gene') :: ['BRMS1'] @entity57911 :: ('1474', 'Gene') :: ['CST6'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis']
@entity5 :: (MESH:D009369,Disease) :: ['tumor']
