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 我们正在从家族性腺瘤性息肉病中建立结直肠癌的预图 （FAP）患者。我们已经建立了一个包含来自78个捐助者的数千个样本的生物库。我们 已经应用了基因组，表观基因组，蛋白质组学，脂肪组，代谢组学，转录组和 空间修饰以表征在从 癌症正常的粘膜。我们建议使用综合方法进一步发展我们的 前任地图集。通过对同一患者的多个息肉进行分析，我们的前批准Atlas启用了 早期事件的表征驱动结直肠癌。我们将： 1）在监视期间，从100个供体的纵向组织样品完全采购 结肠镜检查和预防性手术收集术，包括全血，血清，正常 结肠组织，结肠微生物组，良性癌前息肉，发育不良前息肉 和结肠腺癌。该材料将用于我们自己的中心，也将是 可用于人类肿瘤地图集网络（HTAN）。病历，纵向样本 并且还将收集所有相关的元数据。 2）用最先进的OMICS和成像技术表征组织样品。 3）整合 - 组，成像和医学信息的结果，以构建时空， 多维，综合多摩斯癌地图集，并发展纵向和预测 预科生物学和进展的模型。 4）完成我们建立多派技术的技术，完成我们的法典，snrna-seq 和器官分析。 5）完成大量样本的“多尺度深度数据分析”的出版 来自一些人。使用此信息指导其他数据收集，包括我们的后续数据 - 在器官模型中提高SNRNA-SEQ实验和我们的假设检验实验。 6）确定有助于息肉的因素（例如种系遗传学，免疫功能障碍） 基于这些数据的异质性和建立疾病进展模型。 7）使PCA，HTAN和 一般科学界。