Dataset Information

Cell-free and cell-bound circulating DNA in breast tumours: DNA quantification and analysis of tumour-related gene methylation.

ABSTRACT: Tumour development is characterised by the increased circulating DNA (cirDNA) concentration and by tumour-related changes in blood plasma DNA. Concentration of cirDNA and methylation of RARbeta2, RASSF1A and HIC-1 gene promoters were investigated in cell-free and cell-surface-bound fractions from healthy donors, patients with breast cancer, and patients with breast fibroadenoma. Tumour development was shown to lead to significant changes in the distribution of cirDNA between cell-free and cell-surface-bound fractions. Analysis of RARbeta2 and RASSF1A methylation in the total cirDNA provides 95% diagnostic coverage in breast cancer patients, 60% in patients with benign lesions, and is without false-positive results in healthy women. Results of the study indicate that methylation-specific PCR of RARbeta2 and RASSF1A genes based on the total cirDNA combined with the quantitative analysis of cirDNA distribution between cell-bound and cell-free fractions in blood provide the sensitive and accurate detection and discrimination of malignant and benign breast tumours.

SUBMITTER: Skvortsova TE

PROVIDER: S-EPMC2361269 | biostudies-literature | 2006 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cell-free and cell-bound circulating DNA in breast tumours: DNA quantification and analysis of tumour-related gene methylation.

Skvortsova T E TE Rykova E Y EY Tamkovich S N SN Bryzgunova O E OE Starikov A V AV Kuznetsova N P NP Vlassov V V VV Laktionov P P PP

British journal of cancer 20060501 10

Tumour development is characterised by the increased circulating DNA (cirDNA) concentration and by tumour-related changes in blood plasma DNA. Concentration of cirDNA and methylation of RARbeta2, RASSF1A and HIC-1 gene promoters were investigated in cell-free and cell-surface-bound fractions from healthy donors, patients with breast cancer, and patients with breast fibroadenoma. Tumour development was shown to lead to significant changes in the distribution of cirDNA between cell-free and cell-s ...[more]

PMID: 16641902

Similar Datasets

Project description:Mammography is used to detect breast cancer (BC), but its sensitivity is limited, especially for dense breasts. Circulating cell-free DNA (cfDNA) methylation tests is expected to compensate for the deficiency of mammography. We derived a specific panel of markers based on computational analysis of the DNA methylation profiles from The Cancer Genome Atlas (TCGA). Through training (n = 160) and validation set (n = 69), we developed a diagnostic prediction model with 26 markers, which yielded a sensitivity of 89.37% and a specificity of 100% for differentiating malignant disease from normal lesions [AUROC = 0.9816 (95% CI: 96.09-100%), and AUPRC = 0.9704 (95% CI: 94.54-99.46%)]. A simplified 4-marker model including cg23035715, cg16304215, cg20072171, and cg21501525 had a similar diagnostic power [AUROC = 0.9796 (95% CI: 95.56-100%), and AUPRC = 0.9220 (95% CI: 91.02-94.37%)]. We found that a single cfDNA methylation marker, cg23035715, has a high diagnostic power [AUROC = 0.9395 (95% CI: 89.72-99.27%), and AUPRC = 0.9111 (95% CI: 88.45-93.76%)], with a sensitivity of 84.90% and a specificity of 93.88%. In an independent testing dataset (n = 104), the obtained diagnostic prediction model discriminated BC patients from normal controls with high accuracy [AUROC = 0.9449 (95% CI: 90.07-98.91%), and AUPRC = 0.8640 (95% CI: 82.82-89.98%)]. We compared the diagnostic power of cfDNA methylation and mammography. Our model yielded a sensitivity of 94.79% (95% CI: 78.72-97.87%) and a specificity of 98.70% (95% CI: 86.36-100%) for differentiating malignant disease from normal lesions [AUROC = 0.9815 (95% CI: 96.75-99.55%), and AUPRC = 0.9800 (95% CI: 96.6-99.4%)], with better diagnostic power and had better diagnostic power than that of using mammography [AUROC = 0.9315 (95% CI: 89.95-96.34%), and AUPRC = 0.9490 (95% CI: 91.7-98.1%)]. In addition, hypermethylation profiling provided insights into lymph node metastasis stratifications (p < 0.05). In conclusion, we developed and tested a cfDNA methylation model for BC diagnosis with better performance than mammography.

Dataset Information

Cell-free and cell-bound circulating DNA in breast tumours: DNA quantification and analysis of tumour-related gene methylation.

Publications

Cell-free and cell-bound circulating DNA in breast tumours: DNA quantification and analysis of tumour-related gene methylation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets