A developmental model of sarcomagenesis defines a differentiation-based classification for liposarcomas.
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.
Matushansky
Igor
I
Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University, 1130 St. Nicholas Avenue, New York, NY 10032, USA.
Hernando
Eva
E
Socci
Nicholas D
ND
Matos
Tulio
T
Mills
Joslyn
J
Edgar
Mark A
MA
Schwartz
Gary K
GK
Singer
Samuel
S
Cordon-Cardo
Carlos
C
Maki
Robert G
RG
D050156:Adipogenesis / Q000235:genetics; D054337:Cell Dedifferentiation; D002454:Cell Differentiation; D002478:Cells, Cultured; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D050356:Lipid Metabolism; D008080:Liposarcoma / Q000145:classification* / Q000235:genetics / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000473:pathology; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism
D009363:Neoplasm Proteins