ABSTRACT: Genome wide methylation analysis of breast cancer epithelia, adjacent normal epithelia, breast cancer cell lines, and blood DNA from healthy individuals
Project description:DNA methylation alterations have similar patterns in normal aging tissue and in cancer. In this study, we investigated breast tissue-specific age-related DNA methylation alterations and used those methylation sites to identify individuals with outlier phenotypes. Outlier phenotype is identified by unsupervised anomaly detection algorithms and is defined by individuals who have normal tissue age-dependent DNA methylation levels that vary dramatically from the population mean. To identify age-dependent DNA methylation sites, we generated DNA methylation sequencing data for 29 purified normal adjacent human breast epithelia (age range 33-82 years old) using Digital Restriction Enzyme Analysis of Methylation (DREAM). Next, we validated the age-related sites in publicly available DNA methylation (450K array) of 97 normal adjacent TCGA samples. We found that hypermethylation in normal breast tissue is the best predictor of hypermethylation in cancer. Using unsupervised anomaly detection approaches, we found that about 10% of the individuals (39 /427) were outliers for DNA methylation from 6 publicly available DNA methylation datasets (GSE88883, GSE74214, GSE101961, GSE69914(normal), GSE69914(normal-adjacent), TCGA (Firehose Legacy)). We also found that there were significantly more outlier samples in normal-adjacent to cancer (24/139, 17.3%) then in normal samples (15/228, 5.2%). Additionally, we found significant differences between predicted ages based on DNA methylation and the chronological ages among outliers and not-outliers. Additionally, we found that accelerated outliers (older predicted age) were more frequent in normal-adjacent to cancer (14/17, 82%) compared to normal samples from individuals without cancer (3/17, 18%). Furthermore, in matched samples, the epigenome of the outliers in the pre-malignant tissue was as severely altered as in cancer.
Project description:To define methylation markers of breast cancer for circulating tumor DNA, we compare the methylation characteristics of breast cancer and blood DNA of healthy individuals.
Project description:The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 480,000 CpGs in a total of 407 samples, including 50 normal samples from healthy women, 42 matched normal-adjacent breast cancer pairs (84 samples), 263 unmatched breast cancers, 7 normal samples from BRCA1 carriers and 4 BRCA1 breast cancers. ***WARNING: incomplete metadata supplied for this study***
Project description:The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 480,000 CpGs in a total of 407 samples, including 50 normal samples from healthy women, 42 matched normal-adjacent breast cancer pairs (84 samples), 263 unmatched breast cancers, 7 normal samples from BRCA1 carriers and 4 BRCA1 breast cancers. Bisulphite converted DNA from the 407 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
Project description:Genome wide DNA methylation profiling of tumor adjacent normal tissue from patients with invasive breast cancer, as well as tissue from women undergoing reduction mammoplasty or prophylactic surgery. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,577 CpGs in snap frozen breast tissue. Samples included 70 tumor-adjacent normal breast tissue with invasive disease, 8 tissues from breast prophylactic patients, and 18 tissues from breast reduction patients.
Project description:Genome wide DNA methylation profiling of tumor adjacent normal tissue from patients with invasive breast cancer, as well as tissue from women undergoing reduction mammoplasty or prophylactic surgery. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,577 CpGs in snap frozen breast tissue. Samples included 70 tumor-adjacent normal breast tissue with invasive disease, 8 tissues from breast prophylactic patients, and 18 tissues from breast reduction patients. Bisulphite converted DNA from the 96 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip.
Project description:Both genetic and epigenetic aberrations are linked by intricate crosstalk, and can either individually or in synergy lead to the development of cancer. Accumulating evidence suggests that epigenetic changes such as alterations in DNA methylation play a crucial role in ESCC. We performed a Illumina Infinium HumanMethylation450 BeadChip to examine the global methylation signature of esophageal squamous cell carcinoma of Chinese patients. DNA methylation profiles of esophageal squamous cell carcinoma (4 samples), paired adjacent normal surrounding tissues (4 samples) and normal esophagus mucosa from healthy individuals (4 samples) were generated using Infinium methylation 450K BeadChips from Illumina (Illumina, San Diego, USA).
Project description:Methylation profiles of paired normal adjacent mucosa and tumor samples from 96 individuals and 48 healthy colon mucosae, were obtained through Illumina Infinium Human Methylation 450K BeadChip. This dataset is in the context of the COLONOMICS project and to query additional information you can visit the project website www.colonomics.org.
Project description:The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in whole blood DNA samples from 84 women (42 BRCA1 wild-type and healthy, 7 BRCA1 mutants and healthy, 35 BRCA1 mutants with breast cancer) whole blood DNA from women, with and without breast cancer, and with or without BRCA1 mutation Bisulphite converted DNA from the whole blood samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2 The BRCA1 mutation status represent 0=healthy-brca1wt, 1=healthy-brca1mt, 2=breastcancer-brca1mt.
