Project description:Bilaterality of breast cancer is an indicator of constitutional cancer susceptibility, however, the molecular causes underlying this predisposition in the majority of cases is not known. We hypothesize that epigenetic misregulation of cancer related genes could partially account for this predisposition. We have performed methylation microarray analysis of peripheral blood DNA from 14 women with bilateral breast cancer compared to 14 unaffected matched controls throughout 17 candidate breast cancer susceptibility genes including BRCA1, BRCA2, CHEK2, ATM, ESR1, SFN, CDKN2A, TP53, GSTP1, CDH1, CDH13, HIC1, PGR, SFRP1, MLH1, RARB and HSD17B4. We show that the majority of methylation variability is associated with intragenic repetitive elements. Detailed validation of the tiled region around ATM was performed by bisulfite modification and pyrosequencing of the same samples and in a second set of peripheral blood DNA from 190 bilateral breast cancer patients compared to 190 controls. We show significant hypermethylation of one intragenic repetitive element in breast cancer cases compared to controls (p=0.0017) with the highest quartile of methylation associated with a three-fold increased risk of breast cancer (OR = 3.20, 95% C.I.=1.78-5.86, p=0.000083). Increased methylation of this locus is associated with lower steady state ATM mRNA level and correlates with age of cancer patients but not controls, suggesting a combined age-phenotype related association. This research demonstrates the potential for gene-body epigenetic misregulation of ATM and other cancer related genes in peripheral blood DNA that may be useful as a novel marker to estimate breast cancer risk. Keywords: Differential Methylation Hybridisation
Project description:To identify a set of methylation biomarkers capable of reliably distinguishing breast cancer patients from healthy controls, we performed DNA methylation profiling on germline DNA from peripheral blood samples for a predominantly Asian population comprising 256 ethnic Chinese breast cancer patients recruited from genetic testing clinics and 268 age- and ethnicity-matched non-cancer controls.
Project description:Biomarkers of response are needed in breast cancer to stratify patients to appropriate therapies and avoid unnecessary toxicity. Peripheral blood gene expression and cell type abundance were used to identify biomarkers of response and recurrence in neoadjuvant chemotherapy treated breast cancer patients. Higher peripheral blood monocyte abundance after neoadjuvant chemotherapy was associated with improved prognosis in multiple independent cohorts of breast cancer patients.
Project description:We analyzed gene expression in human peripheral blood mononuclear cells (PBMCs) from breast cancer patients, patients with benign breast abnormalities, healthy cancer-free individuals as well as patients with other types of cancer (gastrointestinal and brain cancers).
Project description:We analyzed gene expression in human peripheral blood mononuclear cells (PBMCs) from breast cancer patients, patients with benign breast abnormalities, healthy cancer-free individuals as well as patients with other types of cancer (gastrointestinal and brain cancers). Peripheral blood mononuclear cell (PBMC) samples were collected from women with a suspect initial mammogram prior to undergoing a diagnostic biopsy procedure to determine whether the detected abnormality was benign or malignant. In total, we collected blood from 57 women with a diagnosis of breast cancer and 37 with a benign diagnosis. We also collected blood from 31 women with normal initial mammograms as negative controls and 15 breast cancer patients following surgery. All breast cancer patient samples were collected at the Duke University Medical Center (DUMC) under an institutional review board (IRB)-approved protocol (Duke eIRB#12025) after obtaining informed consent and were provided by Dr. Jeffrey Marks. PBMC samples from patients with various gastrointestinal cancers (n=15) were colelcted and stored at DUMC under IRB-approved protocols (Duke eIRB#12010 and 12025) and were provided by Dr. Jeffrey Marks. Peripheral blood leukocyte samples from patients with brain tumors (n=7) were provided by Dr. John Sampson and were collected by leukapheresis under Duke eIRB#00003877 and #00009403.
Project description:The ataxia telangiectasia-mutated (ATM) gene is a moderate-risk breast cancer susceptibility gene; germline loss-of-function variants are found in up to 3% of hereditary breast and ovarian cancer (HBOC) families who undergo genetic testing. So far, no clear molecular features of breast tumors occuring in ATM deleterious variant carriers have been described, but identification of an ATM-associated tumors signature may help patients' management. To characterize hallmarks of ATM-associated tumors, absolute copy number variation and loss of heterozygosity profiles were obtained from the OncoScan SNP array.
Project description:We did transcriptomic sequencing of blood samples from 6 breast cancer patients. Total RNA were extracted from peripheral blood and library were constructed for the illumina Xten sequencing. We did transcriptomic sequencing of adjacent normal tissues and cancer tissues from 6 breast cancer patients. Total RNA were extracted and library were constructed for the illumina Xten sequencing.
Project description:Purpose: To infer interactions between circulating breast cancer cells and peripheral mononuclear cells using bioinformatics analysis of single cell RNA-sequencing. Methods: Filter based method for capturing single cells from 7.5mL of blood from patients with breast cancer, followed by single cell RNA-sequencing. Results: Transcriptomes predicted for two CTC populations with distinct expression profiles and interactions with peripheral blood mononuclear cells.