Our overall goal is a compreiiensive molecular genetic and functional analysis of two of the most common soft tissue sarcomas, myxofibrosarcoma (MYXF) and pleomorphic malignant fibrous histiocytoma (PMFH), so as to elucidate the mutational programs and pathways involved in sarcomagenesis and to identify novel therapeutic targets. Tissue samples and cell lines of MYXF and PMFH will be subjected to a multiplatform genome-wide characterization of expression of protein-coding genes and microRNAs, DNA copy number changes, activating mutations, and gene rearrangements. These data will be used to identify both genetically distinct subtypes of MYXF and PMFH and molecular signatures associated with tumor morphology, grade, recurrence, and survival. To identify potential therapeutic targets, we will screen the genes and microRNAs in these signatures for involvement in proliferation, differentiation, and survival of MYXF and PMFH cell lines. Potential targets will be validated by functional assays in additional cell lines and in xenografts. To achieve these goals, we have assembled a multidisciplinary group of investigators armed with 2 unique resources: a database of prospectively collected clinical-pathologic and outcomes data on over 8300 patients treated for soft tissue sarcoma at MSKCC, and a linl

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA140146-04
Application #
8515346
Study Section
Special Emphasis Panel (ZCA1-GRB-I)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$262,919
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
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Argani, Pedram; Reuter, Victor E; Zhang, Lei et al. (2016) TFEB-amplified Renal Cell Carcinomas: An Aggressive Molecular Subset Demonstrating Variable Melanocytic Marker Expression and Morphologic Heterogeneity. Am J Surg Pathol 40:1484-1495
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Kao, Yu-Chien; Sung, Yun-Shao; Zhang, Lei et al. (2016) Recurrent BCOR Internal Tandem Duplication and YWHAE-NUTM2B Fusions in Soft Tissue Undifferentiated Round Cell Sarcoma of Infancy: Overlapping Genetic Features With Clear Cell Sarcoma of Kidney. Am J Surg Pathol 40:1009-20
Moore, Amanda R; Ceraudo, Emilie; Sher, Jessica J et al. (2016) Recurrent activating mutations of G-protein-coupled receptor CYSLTR2 in uveal melanoma. Nat Genet 48:675-80
Huang, Shih-Chiang; Alaggio, Rita; Sung, Yun-Shao et al. (2016) Frequent HRAS Mutations in Malignant Ectomesenchymoma: Overlapping Genetic Abnormalities With Embryonal Rhabdomyosarcoma. Am J Surg Pathol 40:876-85

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