Core 2: Molecular Profiling and Pathology

项目摘要/摘要 分子剖析和病理学(MPP)核心的主要目的是提供 调查人员在这一P01中集中协调资源进行人的分析 肺癌标本、异种移植瘤和其他小鼠模型组织的形态学和免疫组织化学研究 高通量分子方法(组织病理学、免疫组织化学、原位 杂交、基因组分析)。本P01中的MPP核心功能分为四个 有逻辑联系的目标或活动。1.人肺癌组织的采购 验证性研究。核心将作为验证研究的集中资源，使用 根据几个MKSCC IRB批准的方案获取的人类肺癌样本。2. 病理回顾与分析。MPP核心将为组织学和细胞学提供专家 对P01中使用的所有人类肺癌标本进行评估和分类，包括 基于形态的分析(IHC、FISH)。MPP还将提供专家组织病理学审查 基因工程小鼠模型和患者来源的异种人肺肿瘤的研究 免疫缺陷小鼠的肿瘤。3.用于验证的人肺癌组织的基因分型 学习。MPP核心负责监督和管理产生的全面基因组数据 通过使用MSK-IMPACT对MSKCC中发现的所有肺癌进行前瞻性靶向测序 靶向杂交捕获/DNAseq分析和互补靶向RNAseq分析 癌症融合。这项工作提供了所有MSKCC人类的扩展突变注释 对合理的、设计良好的生物学验证研究至关重要的肺肿瘤资源 与研究项目产生的具体线索相关。MPP核心还提供 用于验证研究的FFPE样本的基于纳米串的靶向表达谱分析。4. 使用完全注释的人类肺癌组织进行验证研究的协调。这个 目标1-3中描述的活动提供了大量严格分类的人类 包括所有关键肺癌在内的341多个癌症相关基因的肺癌组织 基因。验证由单个研究项目产生的发现所需的研究 在人类肺癌组织中，将由核心人员或由核心人员协调执行。健壮 建立了DNA、RNA和蛋白质分析的平台，并进行了具体验证 由个人研究需要回答的问题决定的分析 项目。

Project Summary/Abstract The primary purpose of the Molecular Profiling and Pathology (MPP) Core is to provide the investigators in this P01 with a centralized and coordinated resource for the analysis of human lung cancer samples and xenografts and other mouse model tissues using morphologic and high throughput molecular methods (histopathology, immunohistochemistry, in situ hybridization, genomic analyses). The MPP Core functions within this P01 are grouped into four logically connected Aims or activities. 1. Procurement of human lung cancer tissues for validation studies. The Core will serve as the centralized resource for validation studies using human lung cancer samples procured under several MKSCC IRB-approved protocols. 2. Pathology review & analysis. The MPP core will provide expert histologic and cytologic evaluation and classification of all human lung cancer specimens used in the P01, including morphology-based assays (IHC, FISH). The MPP will also provide expert histopathologic review of lung tumors in engineered mouse models as well as patient-derived xenografted human tumors in immunodeficient mice. 3.Genotyping of human lung cancer tissues for validation studies. The MPP Core is overseeing and curating the comprehensive genomic data generated by prospective targeted sequencing of all lung cancers seen at MSKCC using the MSK-IMPACT targeted hybrid capture/DNAseq assay and a complementary targeted RNAseq assay for cancer fusions. This effort providing the extended mutational annotation of all MSKCC human lung tumor resources that is critical for rational, well-designed validation studies biologically relevant to specific leads arising from the Research Projects. The MPP Core also provides NanoString-based targeted expression profiling of FFPE samples for validation studies. 4. Coordination of validation studies using fully annotated human lung cancer tissues. The activities described in Aims 1-3 are providing a rich collection of rigorously classified human lung cancer tissues annotated for over 341 cancer-related genes including all key lung cancer genes. Studies needed to validate the discoveries generated by the individual research projects in human lung cancer tissues will be performed in or coordinated by Core personnel. Robust platforms are established for DNA, RNA and protein analytes, with the specific validation analyses being determined by the questions to be answered by the individual Research Projects.