Matushansky, I., Hernando, E., Socci, N. D., Matos, T., Mills, J., Edgar, M. A., Schwartz, G. K., Singer, S., Cordon-Cardo, C., Maki, R. G. (April 2008) A developmental model of sarcomagenesis defines a differentiation-based classification for liposarcomas. Am J Pathol, 172 (4). pp. 1069-80. ISSN 0002-9440 (Print)0002-9440 (Linking)
Abstract
The importance of adult stem cells in the development of neoplastic diseases is becoming increasingly well appreciated. We hypothesized that sarcomas of soft tissue could be categorized by their developmental/differentiation status from stem cell to mature tissue, similar to the hematological malignancies. We conducted gene expression analyses during in vitro differentiation of human mesenchymal stem cells into adipose tissue, as a representative mature connective tissue, and identified genes whose expression changed significantly during adipogenesis. Gene clustering and distance correlation analysis allowed the assignment of a unique time point during adipogenesis that strongly correlates to each of the four major liposarcoma subtypes. Using a novel gene expression strategy, in which liposarcomas are compared to their corresponding adipocytic maturing cells, we identified a group of genes overexpressed in liposarcomas that indicate the stage of differentiation arrest, ie, sharing a similar expression profile to adipocytic cells at a corresponding stage of differentiation, and a distinct set of genes overexpressed in liposarcomas that are not found in the corresponding stage of differentiation. We propose that the latter set is enriched for candidate transformation-associated genes. Our results indicate that a degree of developmental maturity can be quantitatively assigned to solid tumors, supporting the notion that transformation of a solid tumor stem cell can occur at distinct stages of maturation.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Adipogenesis/genetics Cell Dedifferentiation *Cell Differentiation Cells, Cultured Cluster Analysis Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Immunoblotting Lipid Metabolism Liposarcoma/*classification/genetics/*pathology Mesenchymal Stromal Cells/pathology Models, Biological Neoplasm Proteins/metabolism |
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell differentiation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression diseases & disorders > cancer > cancer types > sarcoma |
| CSHL Authors: | |
| Communities: | CSHL labs > Maki lab |
| Depositing User: | Matt Covey |
| Date: | April 2008 |
| Date Deposited: | 26 Oct 2016 14:17 |
| Last Modified: | 26 Oct 2016 14:17 |
| PMCID: | PMC2276417 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/33689 |
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