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：
8840915
负责人：
David N Hayes
金额：
$ 70万
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/8840915
关键词：
Address Adoption Agreement Base Sequence Biological Assay Biological Markers Cancer Patient Categories Cells Center for Translational Science Activities Characteristics Clinic Clinical Trials Clinical Trials Cooperative Group Clinical Trials Network DNA DNA Sequence DNA Sequence Alteration Decision Making Diagnosis Diagnostic Dideoxy Chain Termination DNA Sequencing Disease Enzymes Freezing Funding Gene Amplification Gene Expression Gene Expression Profile Genes Genetic Transcription Genome Genomics Genotype Goals Grant Health Hereditary Malignant Neoplasm High Prevalence Human Ice Institution Laboratories Laboratory Study Malignant Neoplasms Malignant neoplasm of lung Massive Parallel Sequencing Measures Medicine Methods MicroRNAs Multi-Institutional Clinical Trial Mutation Nucleic Acids Oncogenes Paraffin Paraffin Embedding Pathway interactions Patients Pharmaceutical Preparations Process Production RNA RNA Sequences RNA Viruses Randomized Research Research Personnel Resources Sampling Science Sequence Deletion Services Somatic Mutation Specimen Stratification Syndrome System Techniques Technology U-Series Cooperative Agreements United States National Institutes of Health Untranslated RNA Variant base chromosome loss clinical sequencing clinically actionable cost design exome experience falls genome sequencing improved malignant breast neoplasm meetings nano-string next generation sequencing pathogen personalized medicine prospective skills targeted treatment therapeutic enzyme therapy outcome transcriptome sequencing tumor

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）：在目标治疗时代，实验室研究是癌症临床试验不可或缺的组成部分。连接疗法和结果的最强大的技术之一是使用大量平行测序（MPS）询问核酸（DNA或RNA）的测定法。与种系或结构变化相比，实施了基于核酸的方法，以检测任何体细胞序列改变（“突变”），包括染色体的异常融合，正常DNA序列的丧失（“删除”）或序列重复（“ Amplifications”）。另外，测序测定可以靶向非癌细胞的DNA来解决不同的问题，包括记录完整的参考基因组，家族性癌症综合征的基因分型以及对治疗重要性的药物代谢酶的基因分型。在此提案中提出了一种高度针对性的捕获方法（使用数百个途径基因）。 UNC将从赠款的第一天开始以符合法规的方式提供较高的样品体积临床测序。作为来自冷冻和石蜡包含材料的人类基于人类RNA的癌症测定的世界领导者，包括微阵列，RNA测序和靶向RNA量化，在合规环境中提供了测定。在监管过程中提供专业知识至关重要，以便为治疗决策和患者随机分组提供NGS分析。该提案的目标1和2涉及为高样品吞吐量RNA和符合FDA和帽的机制提供来自多机构合作组临床试验的冷冻或石蜡包含样品的高样品吞吐量RNA和DNA测序。 RNA测序将用于3种格式，RNA-Seq，Nanostring和G-RTPCR，以允许全面的RNA测序和廉价的靶向RNA分析。下一代测序以及通过纳米弹力进行定量DNA测量，将为整个外显子组和靶向捕获提供DNA测序。第三个目的是开发和提供监管服务核心，以加快旨在实施前瞻性临床试验的FDA和CLIA符合性测定法。