Abstract

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

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA140146-05
Application #
8712171
Study Section
Special Emphasis Panel (ZCA1-GRB-I)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
5
Fiscal Year
2014
Total Cost
$268,432
Indirect Cost

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Klein, Mary E; Dickson, Mark A; Antonescu, Cristina et al. (2018) PDLIM7 and CDH18 regulate the turnover of MDM2 during CDK4/6 inhibitor therapy-induced senescence. Oncogene 37:5066-5078
Banito, Ana; Li, Xiang; Laporte, Aimée N et al. (2018) The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma. Cancer Cell 34:346-348
Klein, Mary E; Kovatcheva, Marta; Davis, Lara E et al. (2018) CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought. Cancer Cell 34:9-20
Kao, Yu-Chien; Owosho, Adepitan A; Sung, Yun-Shao et al. (2018) BCOR-CCNB3 Fusion Positive Sarcomas: A Clinicopathologic and Molecular Analysis of 36 Cases With Comparison to Morphologic Spectrum and Clinical Behavior of Other Round Cell Sarcomas. Am J Surg Pathol 42:604-615
Owosho, Adepitan A; Zhang, Lei; Rosenblum, Marc K et al. (2018) High sensitivity of FISH analysis in detecting homozygous SMARCB1 deletions in poorly differentiated chordoma: a clinicopathologic and molecular study of nine cases. Genes Chromosomes Cancer 57:89-95
Suurmeijer, Albert J H; Dickson, Brendan C; Swanson, David et al. (2018) A novel group of spindle cell tumors defined by S100 and CD34 co-expression shows recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes. Genes Chromosomes Cancer 57:611-621
Bennett, Jennifer A; Braga, Ana C; Pinto, Andre et al. (2018) Uterine PEComas: A Morphologic, Immunohistochemical, and Molecular Analysis of 32 Tumors. Am J Surg Pathol 42:1370-1383
Kao, Yu-Chien; Fletcher, Christopher D M; Alaggio, Rita et al. (2018) Recurrent BRAF Gene Fusions in a Subset of Pediatric Spindle Cell Sarcomas: Expanding the Genetic Spectrum of Tumors With Overlapping Features With Infantile Fibrosarcoma. Am J Surg Pathol 42:28-38
Zhang, Jennifer Q; Zeng, Shan; Vitiello, Gerardo A et al. (2018) Macrophages and CD8+ T Cells Mediate the Antitumor Efficacy of Combined CD40 Ligation and Imatinib Therapy in Gastrointestinal Stromal Tumors. Cancer Immunol Res 6:434-447
Fittall, Matthew W; Mifsud, William; Pillay, Nischalan et al. (2018) Recurrent rearrangements of FOS and FOSB define osteoblastoma. Nat Commun 9:2150

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