A Novel Chromosomal Translocation Associated WithCOL1A2-PDGFBGene Fusion in Dermatofibrosarcoma Protuberans

Importance

Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer that develops in the deep dermis to subcutaneous adipose tissues. ACOL1A1-PDGFBgene fusion, leading to the constitutive expression of PDGFB, is the tumorigenic mechanism in most DFSP cases.

Objectives

To evaluate the specificity of PDGFB expression as a diagnostic marker of DFSP and to determine whether other pathomechanisms (ie, gene fusions) exist in patients with DFSP without theCOL1A1-PDGFBfusion gene.

Design, Setting, and Participants

All patients with DFSP registered in the pathologic database of the University of the Ryukyus from January 1, 1997, through December 31, 2013, and Gunma University from January 1, 1996, through December 31, 2011, were included in this analysis. Samples were obtained from 30 patients presenting with DFSP tumors. We examined the clinicopathologic characteristics and the expression of PDGFB, PDGFRβ, PDGFRα, CD34, nestin, factor XIIIa, fibronectin, α–smooth muscle actin, S-100 protein, and Ki-67 in 30 DFSP cases and 48 non-DFSP mesenchymal tumor cases by immunohistochemical analysis. We then analyzed tumor tissues for the presence of theCOL1A1-PDGFBfusion gene. We also tested whether other genes enriched in fibroblasts formed fusion products withPDGFBby reverse transcription–polymerase chain reaction analysis, using gene-specific primers.

Main Outcomes and Measures

We aimed to analyze tumor tissues for the presence of theCOL1A1-PDGFBfusion gene to investigate expression of PDGFB in DFSP tumors.

Results

PDGFB expression was detected in 28 (93%) of 30 patients with DFSP. PDGFB was not homogenously expressed in DFSP tumor cells, whereas CD34 and nestin were often expressed throughout the tumor mass. In 1 DFSP tumor, theCOL1A1-PDGFBfusion gene was not detected even though PDGFB was expressed. We identified a novelCOL1A2-PDGFBfusion gene in this tumor.

Conclusions and Relevance

Our findings indicate that PDGFB protein is expressed in most DFSP tumors and may be a useful diagnostic tool when used in conjunction with CD34 and nestin expression analysis. These PDGFB expression data, in addition to our discovery of a novelPDGFfusion gene, strongly support the concept that DFSP is a PDGFB-dependent tumor type.