COL1A1PDGFB

COL1A1-PDGFB is a fusion gene formed by a chromosomal translocation between COL1A1 on chromosome 17 and PDGFB on chromosome 22, most commonly t(17;22)(q21-25;q13). The fusion combines the COL1A1 promoter and 5' region with the PDGFB coding sequence, leading to constitutive overexpression of PDGF-B. This overproduction promotes signaling through the PDGF receptor beta (PDGFRB), creating an autocrine and paracrine growth stimulus that drives tumor cell proliferation and the activity of surrounding stroma.

Clinical significance: The COL1A1-PDGFB fusion is a defining molecular feature of dermatofibrosarcoma protuberans (DFSP), a rare soft tissue sarcoma characterized by local aggressiveness and a high propensity for local recurrence after treatment. The fusion is detected in the majority of DFSP cases by molecular methods such as fluorescence in situ hybridization (FISH) or reverse transcription PCR, though rare variants with different COL1A1 breakpoints may occur while preserving PDGFB overexpression.

Diagnosis and testing: Immunohistochemistry for CD34 is typically positive in DFSP, supporting the diagnosis, while molecular testing confirms COL1A1-PDGFB to establish the oncogenic driver. FISH break-apart probes or RT-PCR assays are commonly used to identify the fusion.

Treatment implications: Targeted therapy with PDGFR inhibitors, particularly imatinib, has shown activity in unresectable, recurrent, or metastatic DFSP harboring the COL1A1-PDGFB fusion by blocking PDGFR signaling. For localized disease, wide surgical excision is standard, with radiotherapy considered in select cases.