Precancer Atlas of Familial Adenomatous Polyposis

家族性腺瘤性息肉病癌前图谱

• 批准号: 10820046
• 负责人: JAMES M. FORD
• 金额: $ 97.09万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-04 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10820046
• 关键词: 3-Dimensional; Atlases; Automobile Driving; Benign; Biological Assay; Biology; Cancer Etiology; Cells; Cessation of life; Colectomy; Collection; Colon; Colon Adenocarcinoma; Colonoscopy; Colorectal; Colorectal Cancer; Communities; Computer software; Data; Data Analyses; Data Collection; Data Set; Deposition; Development; Dimensions; Disease; Disease Progression; Endoscopy; Event; Familial Adenomatous Polyposis Syndrome; Familial colorectal cancer; Funding; Genetic; Genomics; Heterogeneity; Hi-C; Hospitals; Human; Image; Imaging technology; Immune System Diseases; Individual; Intestines; Lesion; Malignant Neoplasms; Manuscripts; Maps; Medical; Medical Records; Metadata; Methylation; Modeling; Molecular; Mucous Membrane; Mutation; Operative Surgical Procedures; Organoids; Paper; Patients; Persons; Pilot Projects; Polyps; Precancerous Polyp; Proteins; Proteome; Proteomics; Protocols documentation; Publications; Publishing; RNA; Sampling; Serum; Technology; Testing; Text; Tissue Sample; Tissues; United States; Visit; Whole Blood; Work; biobank; colon microbiome; cytokine; data submission; epigenomics; experimental study; follow-up; genome sequencing; lipidome; lipidomics; metabolome; metabolomics; microbiome; molecular imaging; multiple omics; polyposis; predictive modeling; premalignant; prophylactic; recruit; single cell sequencing; single nucleus RNA-sequencing; spatiotemporal; transcriptome; transcriptomics; tumor; tumor progression; tumor-immune system interactions; whole genome

Project Summary We are building a Precancer Atlas of colorectal cancer from Familial Adenomatous Polyposis (FAP) patients. We have built a biobank containing thousands of samples from 78 donors. We have applied genomic, epigenomic, proteomic, lipidomic, metabolomic, transcriptomic, and spatial assays to characterize the molecular changes occurring during the progression from normal mucosa to cancer. We propose to use an integrated approach to further develop our Precancer Atlas. By profiling multiple polyps from the same patient, our Precancer Atlas enables characterization of the early events driving colorectal cancer. We will: 1) Complete procurement of longitudinal tissue samples from 100 donors during surveillance colonoscopy and during prophylactic surgical colectomy, including whole blood, serum, normal colonic tissue, colon microbiome, benign pre-cancerous polyps, dysplastic precancerous polyps and colon adenocarcinomas. The material will be used for our own center and will also be available to the Human Tumor Atlas Network (HTAN). Medical records, longitudinal samples and all relevant metadata will also be collected. 2) Characterize the tissue samples with state-of-the-art omics and imaging technologies. 3) Integrate results from -omics, imaging and medical information, to build a spatiotemporal, multidimensional, integrative multi-omics cancer atlas, and develop longitudinal and predictive models for PreCancer biology and progression. 4) Complete our establishment of multi-omics technologies, finishing our CODEX, snRNA-seq and organoid profiling. 5) Complete the publication of our “multiscale deep data analysis” on a large number of samples from a few people. Use this information to guide additional data collection, including our follow- up snRNA-seq experiments and our hypothesis-testing experiments in organoid models. 6) Identify factors (e.g. germline genetics, immune dysfunction) contributing to polyp heterogeneity and build disease progression models based on these data. 7) Make all biospecimens, information, protocols and software available to the PCA, HTAN and the general scientific community.

项目摘要 我们正在建立一个家族性腺瘤性息肉病结直肠癌癌前病变图谱 (FAP)患者我们已经建立了一个生物银行，包含来自78个捐赠者的数千个样本。我们 已经应用了基因组学、表观基因组学、蛋白质组学、脂质组学、代谢组学、转录组学和 空间分析，以表征从 从正常粘膜到癌症我们建议采用综合方法，进一步发展 癌前病变地图集通过分析同一患者的多个息肉，我们的癌前病变图谱能够 表征导致结直肠癌的早期事件。我们将： 1)在监测期间从100名供体中完成纵向组织样本的采集 结肠镜检查和预防性结肠切除术期间，包括全血、血清、正常 结肠组织，结肠微生物组，良性癌前息肉，发育不良癌前息肉 和结肠腺癌。这些材料将用于我们自己的中心， 人类肿瘤图谱网络（Human Tumor Atlas Network，HTAN）病历、纵向样本 所有相关的元数据也将被收集。 2)使用最先进的组学和成像技术表征组织样本。 3)整合组学、成像和医疗信息的结果，建立一个时空， 多维的，综合的多组学癌症图谱，并开发纵向和预测性的 癌前生物学和进展的模型。 4)完成多组学技术的建立，完成我们的CODEX，snRNA-seq 和类器官分析 5)在大量样本上完成我们的"多尺度深度数据分析"的发表 从几个人那里。使用此信息指导其他数据收集，包括我们的以下内容- snRNA-seq实验和我们在类器官模型中的假设检验实验。 6)确定导致息肉的因素（例如生殖系遗传学、免疫功能障碍） 并基于这些数据建立疾病进展模型。 7)向常设认证机构、HTAN和 一般的科学界。