Network Group Integrated Translational Science Centers Application

网络集团综合转化科学中心申请

基本信息

批准号：
9235259
负责人：
David N Hayes
金额：
$ 69.99万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-22 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9235259
关键词：
Accreditation Address Adoption Biological Assay Biological Markers CLIA certified Cancer Patient Categories Cells Center for Translational Science Activities Characteristics Chromosome abnormality Classification Clinic Clinical Trials Clinical Trials Cooperative Group DNA DNA Sequence DNA Sequence Alteration DNA sequencing Decision Making Diagnosis Diagnostic Dideoxy Chain Termination DNA Sequencing Disease Freezing Funding Gene Amplification Gene Expression Gene Expression Profile Genes Genetic Transcription Genomic medicine Genomics Genotype Goals Grant Hereditary Malignant Neoplasm High Prevalence Human Institution Laboratories Laboratory Study Malignant Neoplasms Malignant neoplasm of lung Massive Parallel Sequencing Measures Methods MicroRNAs Multi-Institutional Clinical Trial Mutation National Clinical Trials Network Nucleic Acids Oncogenes Paraffin Paraffin Embedding Pathway interactions Patients Pharmaceutical Preparations Process Production RNA RNA Viruses Randomized Research Research Personnel Resources Sampling Sequence Deletion Services Somatic Mutation Specimen Stratification Syndrome System Technical Expertise Techniques Technology Testing U-Series Cooperative Agreements United States National Institutes of Health Untranslated RNA Variant base cancer clinical trial chromosome fusion chromosome loss clinical sequencing clinically actionable cost design exome experience falls genome sequencing improved malignant breast neoplasm nano-string next generation sequencing pathogen personalized medicine prospective public health relevance reference genome targeted treatment therapeutic enzyme therapy outcome transcriptome sequencing tumor whole genome

项目摘要

DESCRIPTION (provided by applicant): In the era of targeted therapy, laboratory studies are an integral component of cancer clinical trials. Among the most powerful techniques connecting therapies and outcomes are assays which interrogate nucleic acid (DNA or RNA) using massively parallel sequencing (MPS). Nucleic acid-based approaches are implemented to detect either somatic sequence alterations ("mutations") compared to germline or structural variation including abnormal fusion of chromosomes, loss of normal DNA sequences ("deletions") or sequence duplications ("amplifications"). Alternatively, sequencing assays can target DNA from noncancerous cells to address different questions, including documenting the intact reference genome, genotyping of familial cancer syndromes, and genotyping of drug metabolizing enzymes of therapeutic importance. A highly targeted capture approach (using hundreds of pathway genes) is proposed in this proposal. UNC will provide high sample volume clinical sequencing in a regulatory compliant manner from day one of the grant. As a world leader in the production of human RNA-based cancer assays from both frozen and paraffin-embedded material, including microarrays, RNA sequencing, and targeted RNA quantification, assays are offered within a compliant setting. It is vital to provide expertise in the regulatory process to offer NGS assays prospectively for the purpose of treatment decision-making and patient randomization. Aims 1 and 2 of this proposal involve providing an FDA- and CAP- compliant mechanism for high sample throughput RNA and DNA sequencing from frozen or paraffin-embedded samples provided from multi-institutional cooperative group clinical trials. RNA sequencing will be offered for 3 formats, RNA-Seq, NanoString, and G- rtPCR, to allow both comprehensive RNA sequencing and inexpensive targeted RNA profiling. DNA sequencing will be offered for both whole exome and targeted capture by next generation sequencing as well as quantitative DNA measures by NanoString. The third aim is to develop and provide a regulatory services core to expedite approval for both FDA and CLIA compliant assays designed to be implemented for prospective clinical trials.

描述（由申请人提供）：在靶向治疗时代，实验室研究是癌症临床试验不可或缺的组成部分。连接治疗和结果的最强大技术之一是使用大规模并行测序 (MPS) 来询问核酸（DNA 或 RNA）的检测。基于核酸的方法用于检测与种系相比的体细胞序列改变（“突变”）或结构变异，包括染色体的异常融合、正常DNA序列的丢失（“删除”）或序列重复（“扩增”）。或者，测序分析可以针对非癌细胞的 DNA 来解决不同的问题，包括记录完整的参考基因组、家族癌症综合征的基因分型以及具有治疗重要性的药物代谢酶的基因分型。该提案提出了一种高度针对性的捕获方法（使用数百个途径基因）。从拨款的第一天起，北卡罗来纳大学将以符合监管的方式提供高样本量临床测序。作为利用冷冻和石蜡包埋材料生产基于人类 RNA 的癌症检测（包括微阵列、RNA 测序和靶向 RNA 定量）的世界领先者，检测是在合规的环境中提供的。至关重要的是，在监管过程中提供专业知识，以便前瞻性地提供 NGS 检测，以实现治疗决策和患者随机化的目的。该提案的目标 1 和 2 涉及提供符合 FDA 和 CAP 要求的机制，用于对多机构合作组临床试验提供的冷冻或石蜡包埋样品进行高样品通量 RNA 和 DNA 测序。 RNA 测序将提供 3 种格式：RNA-Seq、NanoString 和 G-rtPCR，以实现全面的 RNA 测序和廉价的靶向 RNA 分析。下一代测序将提供全外显子组和靶向捕获的 DNA 测序，以及 NanoString 的定量 DNA 测量。第三个目标是开发并提供监管服务核心，以加快批准旨在用于前瞻性临床试验的符合 FDA 和 CLIA 的检测。