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(American Journal of Pathology. 2003;163:2383-2395.)
© 2003 American Society for Investigative Pathology

Gene Expression Patterns and Gene Copy Number Changes in Dermatofibrosarcoma Protuberans

Sabine C. Linn*, Rob B. West*, Jonathan R. Pollack*, Shirley Zhu*, Tina Hernandez-Boussard{dagger}, Torsten O. Nielsen{ddagger}, Brian P. Rubin§, Rajiv Patel, John R. Goldblum, David Siegmund||, David Botstein{dagger}, Patrick O. Brown**, C. Blake Gilks{ddagger} and Matt van de Rijn*

From the Departments of Pathology,* Genetics,{dagger} and Biochemistry,** and Howard Hughes Medical Institute, Stanford University Medical Center, Stanford, California; the Department of Statistics,|| Stanford University, Stanford, California; the Department of Pathology{ddagger} and Genetic Pathology Evaluation Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada; the Department of Anatomical Pathology,§ University of Washington Medical Center, Seattle, Washington; and the Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio

Dermatofibrosarcoma protuberans (DFSP) is an aggressive spindle cell neoplasm. It is associated with the chromosomal translocation, t(17:22), which fuses the COL1A1 and PDGFß genes. We determined the characteristic gene expression profile of DFSP and characterized DNA copy number changes in DFSP by array-based comparative genomic hybridization (array CGH). Fresh frozen and formalin-fixed, paraffin-embedded samples of DFSP were analyzed by array CGH (four cases) and DNA microarray analysis of global gene expression (nine cases). The nine DFSPs were readily distinguished from 27 other diverse soft tissue tumors based on their gene expression patterns. Genes characteristically expressed in the DFSPs included PDGFß and its receptor, PDGFRB, APOD, MEOX1, PLA2R, and PRKCA. Array CGH of DNA extracted either from frozen tumor samples or from paraffin blocks yielded equivalent results. Large areas of chromosomes 17q and 22q, bounded by COL1A1 and PDGFß, respectively, were amplified in DFSP. Expression of genes in the amplified regions was significantly elevated. Our data shows that: 1) DFSP has a distinctive gene expression profile; 2) array CGH can be applied successfully to frozen or formalin-fixed, paraffin-embedded tumor samples; 3) a characteristic amplification of sequences from chromosomes 17q and 22q, demarcated by the COL1A1 and PDGFß genes, respectively, was associated with elevated expression of the amplified genes.





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