A developmental model of sarcomagenesis defines a differentiation-based classification for liposarcomas Journal Article


Authors: 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.
Article Title: A developmental model of sarcomagenesis defines a differentiation-based classification for liposarcomas
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. Copyright © American Society for Investigative Pathology.
Keywords: controlled study; human tissue; gene cluster; human cell; cells, cultured; gene overexpression; cluster analysis; gene expression profiling; models, biological; cell maturation; tumor differentiation; neoplasm proteins; cell differentiation; stem cell; sarcoma; gene expression regulation; gene expression regulation, neoplastic; correlation analysis; hematologic malignancy; quantitative analysis; gene identification; immunoblotting; mesenchymal stem cell; cancer classification; malignant transformation; lipid metabolism; liposarcoma; protein isolation; mesenchymal stem cells; connective tissue; cell dedifferentiation; adipogenesis
Journal Title: American Journal of Pathology
Volume: 172
Issue: 4
ISSN: 0002-9440
Publisher: Elsevier Science, Inc.  
Date Published: 2008-04-01
Start Page: 1069
End Page: 1080
Language: English
DOI: 10.2353/ajpath.2008.070284
PUBMED: 18310505
PROVIDER: scopus
PMCID: PMC2276417
DOI/URL:
Notes: --- - "Cited By (since 1996): 17" - "Export Date: 17 November 2011" - "CODEN: AJPAA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Gary Schwartz
    366 Schwartz
  2. Mark Allen Edgar
    45 Edgar
  3. Robert Maki
    211 Maki
  4. Samuel Singer
    233 Singer
  5. Nicholas D Socci
    188 Socci
  6. Tulio A Matos
    2 Matos
  7. Joslyn Mills
    2 Mills