Extension to the HTAN Pre-Cancer Atlas Project

对于许多癌症类型，癌症筛查的广泛采用增加了 癌前病变（PML）的检测。尽管做出了这些努力，但筛查的效果有限 对总体生存率的影响临床指南从观察等待（例如，前列腺）至根治 手术和辅助治疗（例如，乳房）。缺乏可靠的进展风险生物标志物 和模型，这些干预措施可能在两个临床极端产生有害后果： 延误抢救或过度治疗。癌前病变（PML）的研究 分子水平存在重大挑战：PML很小，通常保存在福尔马林中。 此外，任何确定的标志物的临床意义只能在长期随访后评估- 向上，将翻译研究限制为回顾性收集。这些障碍阻止了 精确医学方法和无偏生物标志物的开发和应用， 发展进步的模式。目前的提案将扩大MCL癌前地图集试点 项目（PCAPP于2017年9月启动），目标是建立 来自4个靶器官（肺、乳腺、前列腺）的高度特征性癌前病变 胰腺）。包括的四个器官代表了不同的组织学谱-纯 组织学或混合侵入性病变-和临床设置-治疗或积极监测。 同样，所选的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），但也具有创新性，专注于微 环境和探索空间异质性（多重IHC），对于少数情况， 异质性（单核测序）。拟议的延期将支持完成 的PCAPP，并使一个统一的数据分析和共享与社会。

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.