PDGFB – Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive cutaneous spindle cell neoplasm characterized by infiltrative growth and frequent local recurrence. A pathognomonic somatic rearrangement involving fusion of the collagen type I alpha 1 gene (COL1A1) to the platelet-derived growth factor B gene (PDGFB) drives tumorigenesis in the vast majority of DFSP cases ([PMID:17950782]).

Genetic evidence from a multiplex RT-PCR and FISH analysis of 27 formalin-fixed, paraffin-embedded DFSP specimens revealed COL1A1–PDGFB fusion transcripts in 26/27 tumors, with breakpoints clustering in PDGFB exon 2 and diverse COL1A1 exons, indicating a fusion prevalence of >96% in this cohort ([PMID:17950782]). A larger genomic profiling study of 59 DFSP tumors identified 55 COL1A1::PDGFB fusions alongside rare PDGFD and COL1A2 fusions, confirming structural rearrangements as the primary driver in both primary and metastatic lesions ([PMID:39956270]).

Fusion breakpoint mapping across studies demonstrated COL1A1 breakpoints in exons 7, 10, 29, 40, 46, 49 and various intronic regions, with no correlation to histologic variant, age, or sex, underscoring the mechanistic consistency of PDGFB activation in DFSP pathogenesis ([PMID:17950782]).

Functional characterization of COL1A1–PDGFB fusion proteins shows constitutive activation of the PDGF receptor β, promoting autocrine and paracrine mitogenic signaling. Imatinib mesylate, a PDGFR inhibitor, induces tumor regression in advanced DFSP, although secondary resistance mechanisms—such as additional somatic mutations uncovered by whole-genome sequencing—have been described ([PMID:23922791]).

Integration of genetic and functional data supports a Strong clinical validity classification: recurrent, tumor-specific COL1A1–PDGFB fusions are virtually pathognomonic for DFSP, and targeted inhibition of PDGFR signaling has demonstrated therapeutic efficacy. These findings underpin molecular diagnostics (RT-PCR/FISH) and guide the use of tyrosine kinase inhibitors in DFSP management.

Key Take-home: Detection of COL1A1–PDGFB fusions provides a definitive molecular diagnosis of DFSP and identifies patients likely to benefit from PDGFR-targeted therapy.

References

• Human pathology • 2008 • Dermatofibrosarcoma protuberans COL1A1-PDGFB fusion is identified in virtually all dermatofibrosarcoma protuberans cases when investigated by newly developed multiplex reverse transcription polymerase chain reaction and fluorescence in situ hybridization assays. PMID:17950782
• PLoS One • 2013 • Genetic aberrations in imatinib-resistant dermatofibrosarcoma protuberans revealed by whole genome sequencing. PMID:23922791
• Modern pathology • 2025 • Genomic Profiling Uncovers a Broader Spectrum of Dermatofibrosarcoma Protuberans: Implications for Diagnosis and Therapy. PMID:39956270

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