Integrated Translational Genoproteomics Center at Washington University

描述（由申请人提供）：下一代癌症组学技术正在彻底改变我们对癌症的理解，但我们的临床研究方法却没有跟上步伐。癌症基因组图谱（TCGA）在数据分析方面提供了令人印象深刻的数据和技术进步，但在分析上受到样本积累的不受控制的临床环境的限制。因此，我们建议将华盛顿大学基因组研究所的技术专长与NRG合作小组的累积权力和临床专业知识相匹配，为高通量测序平台产生的大量新数据提供临床和生物学注释。我们还预计，由于NCI对临床蛋白质组学肿瘤分析联盟（CPTAC）的投资，蛋白质组学领域将取得重大技术进步。因此，我们提出了“整合翻译基因蛋白中心”（ITGC），该中心将协同努力将DNA， RNA和肽测序整合到NRG临床试验中，以a)增加我们对常见上皮癌症的生物学理解，b)开发治疗反应的生物标志物，c)确定新的治疗靶点。该提案包括与NRG肿瘤学在乳腺癌、头颈癌、卵巢癌、直肠癌和前列腺癌方面的五个蛋白质基因组试验项目的计划。这些示范项目的目的是将蛋白质基因组学完全整合到术前全身治疗的前瞻性临床试验中，开发用于临床试验资格和分层的基因蛋白质组学分析，并将基于质谱和基于逆相蛋白质阵列（RPPA）的蛋白质组学整合到现有的基因组样本分析管道中。我们的战略目标是将综合发现科学引入合作小组环境。这将促使NRG肿瘤器官委员会更深入地了解他们所治疗的疾病背后的基础生物学，并最终提高正在进行的临床试验假设的质量。

DESCRIPTION (provided by applicant): Next Generation cancer 'omics technologies are revolutionizing our understanding of cancer, but our approaches to clinical investigation have not kept pace. The Cancer Genome Atlas (TCGA) is delivering an impressive body of data and technical advances in data analysis, but is analytically limited by the uncontrolled clinical settings in which the samples were accrued. We therefore propose to match the technical expertise of The Genome Institute at Washington University with the accrual power and clinical expertise of the NRG cooperative group to provide clinical and biological annotation for the vast quantities of new data generated by high-throughput sequencing platforms. We also anticipate major technical advances in the proteomics field as a result of the investment by the NCI in the Clinical Proteomics Tumor Analysis Consortium (CPTAC). We therefore propose the "Integrated Translational Genoproteomlcs Center" (ITGC) that will nucleate a concerted effort to integrate DNA, RNA and Peptide sequencing into NRG clinical trials to a) increase our biological understanding of common epithelial cancers, b) develop biomarkers of treatment response and c) identify new therapeutic targets. This proposal includes plans for five proteogenomic pilot projects with NRG Oncology In breast cancer, head and neck cancer, ovarian cancer, rectal cancer and prostate cancer. The aims of these demonstration projects are to fully integrate proteogenomics into prospective clinical trials of preoperative systemic therapy, to develop genoproteomic assays for clinical trial eligibility and stratification and to integrate mass-spectrometry-based and reverse phase protein array-based (RPPA) proteomics into the existing genomic sample analysis pipeline. Our strategic objective is to bring comprehensive discovery science into the cooperative group setting. This will drive the NRG Oncology organ site committees to more deeply appreciate the fundamental biology that underlies the diseases that they treat and should ultimately raise the quality of the clinical trial hypotheses that are pursue. RELEVANCE: The integration of DNA, RNA and Peptide sequencing-based discovery science into cooperative group trials is our goal. This will stimulate biomarker research that will drive te development of laboratory tests required for our long-term goal of a tumor etiology-matched therapeutics program that improves outcomes for a broad spectum of patients diagnosed with common epithelial malignancies.