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Ultrasensitive Detection of Tumor Specific DNA Methylation Changes for the Early Detection of Lung Cancer

超灵敏检测肿瘤特异性 DNA 甲基化变化以早期发现肺癌

基本信息

批准号：
9353351
负责人：
JAMES G. HERMAN
金额：
$ 58.14万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
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：
2016-09-15 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9353351
关键词：
Address Apoptotic Benign Biological Biological Assay Biological Markers Biomedical Engineering Blood Blood specimen Body Fluids Cancer Detection Cancer Etiology Cessation of life Clinical Communities Complement DNA DNA Markers DNA Methylation DNA Sequence Data Detection Diagnosis Diagnostic Early Detection Research Network Early Diagnosis Eligibility Determination Enrollment Epigenetic Process Evaluation Event Frequencies Genes Genetic Genomics Guidelines High Prevalence Lesion Lung Lung Neoplasms Lung nodule Malignant Neoplasms Malignant neoplasm of lung Measures Methods Methylation Microfluidics Molecular Molecular Analysis Monitor Necrosis Nucleic Acids Participant Patients Performance Plasma Population Predictive Value Preparation Process Prospective cohort Proteomics Radiology Specialty Recruitment Activity Registries Reporting Reproducibility Research Infrastructure Resolution Sampling Screening for cancer Sensitivity and Specificity Silicon Dioxide Smoker Specificity Specimen Sputum Techniques Testing The Cancer Genome Atlas Time United States United States Centers for Medicare and Medicaid Services X-Ray Computed Tomography anticancer research base biomarker development bisulfite cancer biomarkers cancer epidemiology cancer genome cell free DNA circulating DNA clinically relevant cohort digital genome-wide analysis high risk population improved laboratory development low-dose spiral CT lung cancer screening melting mortality nanomembrane neoplastic cell noninvasive diagnosis novel personalized medicine population based prospective sample collection screening tumor tumor DNA tumorigenesis

项目摘要

TITLE Ultrasensitive Detection of Tumor Specific DNA Methylation Changes for the Early Detection of Lung Cancer ABSTRACT This proposal seeks to improve upon the management of lung cancer through detection of tumor specific abnormal DNA methylation. Despite highly publicized advances in genomics and proteomics, the promise of non-invasive diagnostics and personalized medicine remains largely unrealized. Recently, comprehensive determination of genetic and epigenetic aberrations has become a major activity in cancer research since it is well understood that these aberrations provide clues to the process of tumorigenesis. The applicants have developed extremely sensitive assays for the detection of hypermethylated DNA sequences. They have also optimized the isolation and processing of circulating cell free DNA from tumors for these sensitive methods. The comprehensive genome wide analysis of molecular changes in cancer completed by The Cancer Genome Atlas (TCGA) has been used to identify many highly frequent cancer specific methylation events in lung cancer that will be combined with an integrated approach to sample processing and preparation and novel sensitive detection strategies to provide utrasensitive detection of tumor specific changes in DNA methylation in blood and sputum samples. With a large population based screening cohort, the Pittsburgh Lung Screening Study, they will develop and characterize the performance of sensitive methods for detecting cancer specific changes in DNA methylation. This molecular detection will compliment CT screening to address the important issue of early detection of lung cancer.

标题超灵敏检测肿瘤特异性DNA甲基化改变早期检测肿瘤细胞凋亡肺癌摘要这项建议旨在通过检测肺癌，肿瘤特异性异常DNA甲基化。尽管基因组学的进步得到了高度宣传，蛋白质组学、非侵入性诊断和个性化医疗的前景在很大程度上仍然是未实现。最近，遗传和表观遗传畸变的综合测定已成为一种新的方法。成为癌症研究的主要活动，因为众所周知，这些畸变为肿瘤的发生提供线索。申请人已经发展到了用于检测高甲基化DNA序列的灵敏测定。他们还优化了来自肿瘤的循环无细胞DNA的分离和处理，敏感方法。癌症分子变化的全基因组分析由癌症基因组图谱（TCGA）完成，已用于识别许多高度肺癌中频繁的癌症特异性甲基化事件，样品处理和制备的集成方法以及新的灵敏检测提供超灵敏检测肿瘤特异性DNA甲基化变化的策略血液和痰液样本由于有一个大的基于人群的筛查队列，匹兹堡肺筛查研究，他们将开发和表征敏感方法的性能用于检测DNA甲基化中的癌症特异性变化。这种分子检测将补充CT筛查，以解决早期发现肺癌的重要问题。