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, Torsten O. Nielsen, Brian P. Rubin, Rajiv Patel, John R. Goldblum, David Siegmund, David Botstein, Patrick O. Brown, C. Blake Gilks, Matt Van De Rijn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

121 Citations (Scopus)

Abstract

Dermatofibrosarcoma protuberans (DFSP) is an aggressive spindle cell neoplasm. It is associated with the chromosomal translocation, t(17:22), which fuses the COL1A1 and PDGFβ 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 PDGFβ 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 PDGFβ, 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 PDGFβ genes, respectively, was associated with elevated expression of the amplified genes.

Original languageEnglish
Pages (from-to)2383-2395
Number of pages13
JournalAmerican Journal of Pathology
Volume163
Issue number6
DOIs
Publication statusPublished - Dec 2003
Externally publishedYes

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