of Core Service Plan: The primary purpose ofthe Molecular Profiling and Pathology (MPP) Core is to provide the investigators in this POl with a centralized and coordinated resource for the analysis of human lung cancer samples and animal model tissues using morphologic and high throughput molecular methods (histopathology, immunohistochemistry, in situ hybridization, genomic and proteomic analyses). The MPP Core functions within this POl 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 IRBapproved protocols. For rebiopsy protocols (non-therapeutic rebiopsy after treatment initiation or rebiopsy upon progression due to presumed acquired resistance), the Gore will also serve as the main tissue repository. 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 POl, including morphologybased assays (IHC, GISH, FISH). The MPP will also provide expert histopathologic review of lung tumors in mouse models as well as xenografted human tumors. 3. Genotyping of human lung cancer tissues for validation studies. The MPP Gore has established and is further developing prospective genotyping efforts to provide extended mutational annotation of its human lung tumor resources that is critical for rational, welldesigned validation studies biologically relevant to specific leads arising from the Research Projects. 4. Coordination of validation studies using fully annotated human lung cancer tissues. The activities described in Aims 1-3 will provide a rich collection of rigorously classified human lung cancer tissues annotated for 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.

Public Health Relevance

The MPP core will serve a critical validation function, relating the findings ofthe Research Projects to human lung carcinomas and placing them in the context of key clinical, pathologic, mutational, and genomic parameters. Consistency of diagnostic criteria and technical platforms will ensure data comparability and data exchange between projects.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA129243-07
Application #
8563897
Study Section
Special Emphasis Panel (ZCA1-RPRB-J)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
7
Fiscal Year
2013
Total Cost
$199,697
Indirect Cost
$69,101
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Mo, Qianxing; Shen, Ronglai; Guo, Cui et al. (2018) A fully Bayesian latent variable model for integrative clustering analysis of multi-type omics data. Biostatistics 19:71-86
Childress, Merrida A; Himmelberg, Stephen M; Chen, Huiqin et al. (2018) ALK Fusion Partners Impact Response to ALK Inhibition: Differential Effects on Sensitivity, Cellular Phenotypes, and Biochemical Properties. Mol Cancer Res 16:1724-1736
Gao, Yijun; Chang, Matthew T; McKay, Daniel et al. (2018) Allele-Specific Mechanisms of Activation of MEK1 Mutants Determine Their Properties. Cancer Discov 8:648-661
Arbour, Kathryn C; Jordan, Emmett; Kim, Hyunjae Ryan et al. (2018) Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer. Clin Cancer Res 24:334-340
Gallant, Jean-Nicolas; Lovly, Christine M (2018) Established, emerging and elusive molecular targets in the treatment of lung cancer. J Pathol 244:565-577
Hellmann, Matthew D; Nathanson, Tavi; Rizvi, Hira et al. (2018) Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer. Cancer Cell 33:843-852.e4
Yao, Zhan; Gao, Yijun; Su, Wenjing et al. (2018) RAF inhibitor PLX8394 selectively disrupts BRAF dimers and RAS-independent BRAF-mutant-driven signaling. Nat Med :
Suzawa, Ken; Offin, Michael; Lu, Daniel et al. (2018) Activation of KRAS Mediates Resistance to Targeted Therapy in MET Exon 14-mutant Non-small Cell Lung Cancer. Clin Cancer Res :
Yu, Helena A; Planchard, David; Lovly, Christine M (2018) Sequencing Therapy for Genetically Defined Subgroups of Non-Small Cell Lung Cancer. Am Soc Clin Oncol Educ Book :726-739
Yuan, Tina L; Amzallag, Arnaud; Bagni, Rachel et al. (2018) Differential Effector Engagement by Oncogenic KRAS. Cell Rep 22:1889-1902

Showing the most recent 10 out of 188 publications