title: Molecular and clinicopathological analysis of dermatofibrosarcoma protuberans.
abstract: Dermatofibrosarcoma protuberans (DFSP) is a dermal and subcutaneous tumor of intermediate malignancy. The most remarkable cytogenetic feature of DFSP is the chromosomal translocation t(17;22)(q22;q13), causing a fusion of the platelet-derived growth factor beta chain (PDGFB) gene at 22q13, and the collagen type 1 alpha 1 (COL1A1) at 17q22. The aim of the study was to analyze the molecular characteristic of DFSP in conjunction with histopathological and clinical features. We performed fluorescence in situ hybridization (FISH) and multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) to detect chromosomal translocations and fusion gene transcripts in 16 formalin-fixed, paraffin-embedded DFSP samples. In addition, the amplification of PDGFB was also evaluated in the 16 DFSP samples by real-time PCR. FISH analysis revealed that all the 16 samples exhibited COL1A1-PDGFB gene fusion. Eleven out of 11 informative cases (100%) showed fusion transcripts by multiplex RT-PCR analysis. Various exons of the COL1A1 gene were fused with the PDGFB gene. Among them, exon 25 was found to be more frequently involved. Real-time PCR showed that the PDGFB copy number increase in the DFSP samples was higher than in normal skin tissues (p=0.007). Values of FISH fusion signals and PDGFB DNA analysis were variable between samples, but suggested that increased values might be associated with parameters of tumor progression. Our results confirm that analysis of the COL1A1-PDGFB status by FISH and RT-PCR is a useful tool in the confirmation of a DFSP diagnosis. In addition, the analysis of PDGFB copy number status may become a useful diagnostic marker since the gene is a potential target for treatment of DFSP patients.
authors.affiliation: Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University Jena, Ziegelmühlenweg 1, Jena, Germany.
authors.forename: Kassandra
authors.initials: K
authors.lastname: Walluks
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Cornelius
authors.initials: C
authors.lastname: Woelfel
authors.forename: Linlin
authors.initials: L
authors.lastname: Yang
authors.forename: Tiantian
authors.initials: T
authors.lastname: Cui
authors.forename: Claudia
authors.initials: C
authors.lastname: Seliger
authors.forename: Christiane
authors.initials: C
authors.lastname: Geier
authors.forename: Thomas
authors.initials: T
authors.lastname: Knösel
authors.forename: Sven
authors.initials: S
authors.lastname: Hauke
authors.forename: Iver
authors.initials: I
authors.lastname: Petersen
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D018223:Dermatofibrosarcoma / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D020571:Genes, sis / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D015514:Oncogene Proteins, Fusion