Analysis of microsatellite instability using Promega panel in dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a rare neoplasm derived from fibroblasts. Although the frequency of microsatellite instability (MSI) in skin cancer is reported to be less than 5%, there is only one report of the status of MMR in DFSP. The only analytical report of microsatellite stability in which Promega panel is not used, showed that the frequency of MSI-high, MSI-low and microsatellite stable (MSS) cases was 13.9% (5/36), 16.7% (6/36) and 69.4% (25/36), respectively. Thus, the aim of this study was to evaluate the status of MMR in 36 patients with DFSP diagnosed at Kumamoto University. MSI analysis using the Promega panel showed that all cases were MSS, which indicated the absence of MSI in DFSP. This result indicates that the status of MMR may not be useful for the potential therapeutic application of pembrolizumab and the pathogenesis of DFSP may not involve MSI.

Establishment of novel patient-derived models of dermatofibrosarcoma protuberans: two cell lines, NCC-DFSP1-C1 and NCC-DFSP2-C1.

Dermatofibrosarcoma protuberans (DFSP) is a common type of dermal sarcoma, characterized by the presence of the unique collagen type I alpha 1 chain (COL1A1)-PDGFB translocation, which causes constitutive activation of the platelet-derived growth factor ß (PDGFB) signaling pathway. Patients with DFSP exhibit frequent local recurrence, and novel therapeutic approaches are required to achieve better clinical outcomes. Patient-derived cancer cell lines are essential in the preclinical research. Here, we established novel patient-derived DFSP cell lines from two patients with DFSP and designated these cell lines NCC-DFSP1-C1 and NCC-DFSP2-C1. Tumors of the two patients with DFSP had COL1A1-PDGFB translocations with distinct COL1A1 breakpoints, e.g., in exons 33 and 15, and the translocations were preserved in the established cell lines. NCC-DFSP1-C1 and NCC-DFSP2-C1 cells exhibited similar morphology and limited capability of proliferation in vitro, forming spheroids when seeded on low-attachment tissue culture plates. In contrast, NCC-DFSP1-C1 cells had considerably higher invasive capability than NCC-DFSP2-C1 cells. Overall proteome contents were similar between NCC-DFSP1-C1 and NCC-DFSP2-C1 cells. Notably, in vitro screening studies identified anticancer drugs that showed antiproliferative effects at considerably low concentrations in the DFSP cell lines. Bortezomib, mitoxantrone, ponatinib, and romidepsin were more cytotoxic to NCC-DFSP1-C1 cells than to NCC-DFSP2-C1 cells. These cell lines will be useful tools for developing novel therapeutic strategies to treat DFSP.