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.