Extension to the HTAN Pre-Cancer Atlas Project

HTAN 癌前图谱项目的扩展

• 批准号: 10269615
• 负责人: E.Shelley Hwang
• 金额: $ 30.46万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-08 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10269615
• 关键词: Accounting; Address; Adjuvant; Administrator; Adoption; Archives; Atlases; Automobile Driving; Biological; Biological Assay; Biological Markers; Breast; Budgets; Cancer Center; Cell Count; Cell Nucleus; Cells; Clinical; Cloud Computing; Collaborations; Collection; Communities; Complex; Computational Biology; Consult; Consultations; Contracts; Copy Number Polymorphism; Core Facility; DNA; DNA Sequence Alteration; DNA analysis; Data; Data Analyses; Databases; Detection; Development; Ensure; Epithelial; Epithelial-Stromal Communication; Event; Formalin; Gene Expression; Gene set enrichment analysis; Generations; Genes; Genomics; Genotype; Goals; Guidelines; Health Insurance Portability and Accountability Act; Heterogeneity; High-Throughput Nucleotide Sequencing; Histologic; Histology; Human; Image Analysis; Immune; Immunohistochemistry; Intervention; Invasive Lesion; Laboratories; Lead; Lesion; Lesion by Morphology; Libraries; Life; Logistics; Lung; Malignant Neoplasms; Methods; Methylation; Mitotic; Modeling; Molecular; Mutation; Mutation Analysis; Necrosis; Operative Surgical Procedures; Organ; Pancreas; Papillary; Pathogenicity; Pathology; Patient observation; Pilot Projects; Postdoctoral Fellow; Preparation; Prevalence; Process; Prostate; RNA; RNA analysis; Regulation; Resolution; Resources; Risk; Sampling; Savings; Scanning; Screening for cancer; Services; Signal Transduction; Slide; Solid; Specific qualifier value; Standardization; Students; System; T-Cell Proliferation; Testing; Tissue Stains; Tubular formation; Tumor-infiltrating immune cells; Validation; Work; biomedical informatics; cancer genomics; cancer type; cell type; clinically significant; computer center; computerized data processing; data integration; data sharing; data standards; database of Genotypes and Phenotypes; design; driver mutation; exome; experimental study; follow-up; innovation; member; multimodality; mutational status; novel; overtreatment; precision medicine; premalignant; prevent; quantitative imaging; random forest; scale up; screening; sequencing platform; single-cell RNA sequencing; targeted sequencing; tissue processing; transcriptome; translational study; tumor; whole genome

For many cancer types, the wide-spread adoption of cancer screening has increased the detection of pre-malignant lesions (PML). Despite such efforts, screening has had limited impact on overall survival. Clinical guidelines vary widely from watchful waiting (e.g., prostate) to radical surgery and adjuvant treatment (e.g., breast). In absence of reliable progression risk biomarkers and models, these interventions may have deleterious consequences at the two clinical extremes: delay in life-saving treatment or overtreatment. The study of pre-malignant lesions (PML) at molecular level present significant challenges: PML are small, generally archived in formalin. Moreover, the clinical significance of any identified marker can only be assessed after long follow- up, limiting the translational studies to retrospective collections. These hurdles have prevented the development and application of precision medicine approaches and unbiased biomarker to develop models of progression. The current proposal will extend the MCL Pre-Cancer Atlas Pilot Project (PCAPP initiated in September 2017) with the goal to build multi-modal profiles of highly characterized pre-malignant lesions from the 4 target organs (Lung, Breast, Prostate and Pancreas). The four organs included represent a diverse spectrum of histology - pure histology or mixed with invasive lesions - and clinical settings - treatment or active surveillance. Similarly, the selected profiling methods are as comprehensiveas for invasive tumors atlas (whole transcriptome gene expression or DNA mutations) but also innovative, focusing on micro- environment and exploring spatial heterogeneity (multiplex IHC) and, for a few cases, cellular heterogeneity (single-nuclei sequencing). The propose extension will support the completion of the PCAPP and enable a uniform data analysis and sharing with the community.

对于许多癌症类型，癌症筛查的广泛采用增加了 癌前病变检测(PML)。尽管做出了这些努力，但筛查的效果有限。 关于整体生存的问题。临床指南差异很大，从警惕的等待(例如，前列腺)到根治 手术和辅助治疗(如乳房)。在缺乏可靠的进展风险生物标志物的情况下 和模型，这些干预措施可能在两个临床极端产生有害后果： 延误救命治疗或过度治疗。癌前病变(PML)的研究进展 分子水平面临着巨大的挑战：PML很小，通常保存在福尔马林中。 此外，任何已识别的标志物的临床意义只有在长期随访后才能评估。 UP，将翻译研究限制在追溯性收藏。这些障碍阻碍了 精准医学方法和无偏生物标志物的开发与应用 发展进步的模型。目前的提议将延长MCL癌症前图谱试点 项目(PCAPP于2017年9月启动，目标是建立多模式配置文件 4个靶器官(肺、乳腺、前列腺)的高度特征性癌前病变 和胰腺)。其中的四个器官代表了不同的组织学领域--纯的 组织学或混合侵袭性病变--和临床环境--治疗或积极监测。 同样，选定的概况分析方法与侵袭性肿瘤图谱(整体)一样全面 转录组基因表达或DNA突变)，但也有创新，专注于微观 环境和探索空间异质性(多重IHC)，在少数情况下，细胞 异质性(单核测序)。拟议的延期将支持完成 PCAPP并实现统一的数据分析和与社区共享。