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Heterogeneity of DNA methylomes between circulating tumor cells

循环肿瘤细胞之间 DNA 甲基化组的异质性

基本信息

批准号：
9261124
负责人：
Veronica Ortiz
金额：
$ 4.3万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-12-01 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9261124
关键词：
Address Area Bioinformatics Biological Markers Biology Brain Breast Cancer Patient Breast Cancer cell line Breast cancer metastasis Cardiovascular system Cell Line Cells Cessation of life Characteristics Clonal Expansion CpG Islands CpG dinucleotide Cytosine DNA DNA Methylation DNA Sequence Data Databases Development Disease Progression Distant Doctor of Philosophy Enhancers Epigenetic Process Evolution Extracellular Matrix Gene Expression Genes Genetic Transcription Genomic DNA Genomics Genotype Heterogeneity Individual Lead Link Literature Lung Malignant Neoplasms Measures Methylation Mutate Neoplasm Circulating Cells Neoplasm Metastasis Oncogenes Organ Outcome Patients Pattern Phenotype Population Positioning Attribute Primary Neoplasm Protocols documentation Publishing Repression Sequence Analysis Sorting - Cell Movement The Cancer Genome Atlas Time Transcript Tropism Tumor Cell Line United States Variant Woman abstracting base bisulfite sequencing bone cancer cell cohort interest malignant breast neoplasm matrigel metastasis prevention methylation pattern methylome mouse model novel outcome forecast programs public health relevance single cell analysis transcriptome sequencing tumor whole genome

项目摘要

Project Summary/Abstract Breast cancer is the most prevalent cancer among women and leads to about 40,000 metastatic related deaths annually in the United States. Circulating tumor cells (CTCs) shed from the primary tumor into the circulatory system. These CTCs are then displaced in distant organs where metastatic tumors eventually arise. Distinctive breast cancer CTCs are assumed to result from discrete patterns of mutated cancer genes. Nonetheless, the contribution of epigenetic changes to the development of individual CTC characteristics is unknown. DNA methylation at cytosines in CpG dinucleotides is critical in programming gene expression and its disruption is a typical hallmark of cancer. Vertebrate CpG islands are short spreads of DNA sequences that differ from the typical genomic pattern by being GC-rich and predominantly unmethylated. In cancer cells, some CpG islands become strongly methylated, which results in repression of gene transcription. Additionally, partially methylated domains (PMDs) are found in gene poor regions which correspond to lamina-attachment domains. PMDs are thought to be linked to gene expression, but not enough is known about why their corresponding domains exist or about their single cell composition. Methylomes have also been linked to enhancers that control a cohort of gene expression. Our lab has established several patient-derived CTC lines, allowing me to analyze the methylomes in CTCs for the first time. By studying the methylomes of CTCs using whole genome bisulfite sequencing (WGBS), I hope to understand if methylation patterns in CTCs are heterogeneous and how this variation contributes to metastasis. Findings from WGBS analysis have demonstrated that the CTC lines Brx50 and Brx61 appear to be less methylated when compared to the CTC lines Brx07 and Brx68. Intriguingly, Brx07 and Brx68 are more metastatic when compared to Brx50 and Brx61. These specific areas that vary between the CTCs’ methylomes could be potential areas of interest for metastasis.

项目总结/文摘