Center for Advanced Multi-Omic Characterization of Cancer

项目总结 国家癌症研究所的临床蛋白质组肿瘤分析联盟(CPTAC)是一项全国性的努力，以 通过大规模蛋白质组的应用促进对癌症分子基础的理解 和基因组分析，或蛋白质组学。CPTAC成立于2011年，开创了整合蛋白质基因组学的先河 对结直肠癌、乳腺癌和卵巢癌的分析，以揭示对这些癌症类型的新见解，例如 通过拷贝相关分析鉴定蛋白质组中心亚型，确定驱动突变的优先顺序 数量变化和蛋白质丰度，并通过后研究了解与癌症相关的途径 翻译修饰语。 在这个项目中，CPTAC将与NIH共同基金加布里埃拉·米勒儿童第一儿科合作 全面鉴定儿童白血病样本(如T细胞)的研究计划(儿童优先) 急性淋巴细胞白血病(T-ALL)和急性髓系白血病(AML) 蛋白质组学。该项目将充分整合此类白血病样本的蛋白质基因组信息，以捕获和 复制特定的癌症表型，更好地了解癌症途径的相互联系，识别新的 靶向治疗和免疫治疗的蛋白质靶点，并刺激未来的儿科癌症研究 和精确肿瘤学。 PNNL PCC将进行全面的、集成的全球蛋白质组和磷酸蛋白质组分析 由儿童第一合作者以各种形式(如细胞)提供的总计272个儿童白血病样本 小球和表面样品)，使用最先进的液相色谱-串联质谱仪 仪器、高度多样化的等压质量标记(TMT 18-plex)和集成样品 工作流程。由此产生的分子数据将成为CAVATICA可用的社区资源。

PROJECT SUMMARY The National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) is a national effort to accelerate the understanding of the molecular basis of cancer through the application of large-scale proteome and genome analysis, or proteogenomics. Launched in 2011, CPTAC pioneered the integrated proteogenomic analysis of colorectal, breast and ovarian cancer to reveal new insights into these cancer types, such as identification of proteomic-centric subtypes, prioritization of driver mutations by correlative analysis of copy number alterations and protein abundance, and understanding cancer-relevant pathways through post- translational modifications. In this project, CPTAC will collaborate with the NIH Common Fund Gabriella Miller Kids First Pediatric Research Program (Kids First) to comprehensively characterize pediatric leukemia samples (such as T-cell acute lymphoblastic leukemia, T-ALL, and acute myeloid leukemia, AML) using mass spectrometry-based proteomics. This project will fully integrate proteogenomic information of such leukemia samples to capture and replicate specific cancer phenotype, better understand the interconnection of cancer pathways, identify novel protein targets for targeted therapies and immunotherapies, and to stimulate future pediatric cancer research and precision oncology. The PNNL PCC will perform comprehensive, integrated global proteome and phosphoproteome analyses of a total of 272 pediatric leukemia samples provided by the Kids First collaborators in various forms (such as cell pellets and surfaceome samples), using state-of-the-art liquid chromatography-tandem mass spectrometry instrumentation, highly multiplexed isobaric mass-tag labeling (TMT 18-plex), and integrated sample workflows. The resulting molecular data will become a community resource available at CAVATICA.