Determination of COL1A1-PDGFB breakpoints by next-generation sequencing in the molecular diagnosis of dermatofibrosarcoma protuberans.

Objective: In most cases, dermatofibrosarcoma protuberans (DFSP) is characterized by the chromosomal translocation t (17; 22) (q22; q13) that leads to a fusion of collagen type 1 alpha 1 (COL1A1) and platelet-derived growth factor beta chain (PDGFB). Recently, next-generation sequencing (NGS) has been reported to detect fusion transcripts in some malignancies. Therefore, the present study aimed to evaluate the utility of the targeted NGS in detecting the COL1A1-PDGFB fusion in patients with DFSP.

Methods: We designed a targeted DNA capture panel to tile along the fusion regions, including exon, intron, and untranslated regions of the COL1A1 and PDGFB. A cohort of 18 DNA samples extracted from formalin-fixed, paraffin-embedded tissues was used to evaluate the targeted NGS. The results were compared with that of fluorescence in situ hybridization (FISH).

Results: The COL1A1-PDGFB fusion was identified in 13 of 18 cases (72.2%) by targeted NGS assay. PDGFB breakpoints were constantly found in exon 2, while breakpoints in COL1A1 varied from exon 15 to 46. Of these 18 cases assayed by FISH, 12 (66.7%) exhibited COL1A1-PDGFB fusion signals. One case (P9), which was FISH-negative, was demonstrated with the fusion by targeted NGS and validated by PCR and Sanger sequencing. The targeted NGS results showed a high concordance with the results of the FISH assay (94.4%).

Conclusion: Our study reported a targeted NGS assay for detecting the breakpoints of the COL1A1-PDGFB fusion gene, which can be implemented in diagnosing patients with DFSP.