Dermato®brosarcoma protuberans (DP), an in®ltrative skin tumour of intermediate malignancy, presents speci®c cytogenetic features such as reciprocal translocations t(17;22)(q22;q13.1) or supernumerary ring chromosomes derived from t(17;22). We have previously shown that both rings and translocated chromosomes derived from t(17;22) presented the same molecular rearrangement with fusion of the COL1A1 gene on chromosome 17 to the PDGFB gene on chromosome 22. To study the structure and function of the COL1A1 ± PDGFB chimeric protein, we used a tumour-derived chimeric COL1A1 ± PDGFB cDNA to perform stable and transient transfections in the Chinese hamster lung ®broblastic cell line PS200 and the human epithelial cell line HEK293. We demonstrated that the stably transfected clones that expressed the COL1A1 ± PDGFB chimeric protein became growth factors independent and tumorigenic in nude mice. In addition, COL1A1 ± PDGFB transfected cell supernatants signi®cantly stimulated ®broblastic cell growth, through the activation of the PDGFB receptor pathway. By using anti-PDGFB and speci®c anti-COL1A1 ± PDGFB antibodies, we showed that, similar to PDGFB, the COL1A1 ± PDGFB chimeric proteins are processed in transfected cells into mature PDGFB dimers. These results strongly suggest that the COL1A1 ± PDGFB chimeric gene expression associated with DP, induces tumours formation through production of mature PDGFB, in an autocrine or paracrine way. Strikingly, mutagenesis experiments indicated that uncleaved COL1A1 ± PDGFB forms are mitogenic and therefore could contribute, as well as mature PDGFB, to the establishment of a transformed phenotype. Oncogene (2001) 20, 2965 ± 2975.