t(17;22)(q22;q13) is found in most if not all Dermatofibrosarcoma Protuberans cases

Rare soft tissue tumor, accounts for up to 1% of all soft tissue sarcomas.

Typically diagnosed in young to middle-aged adults and affects either sex and all races, however numerous pediatric and congential cases have been reported. The duration of the lesions prior to diagnosis is commonly more than 5 years, and decades in some cases.

Monotonous storiform pattern of uniform, cytologically bland spindle cells, with a characteristic honeycomb pattern of infiltration into the subcutaneous fat. Immunohistochemical staining demonstrates strong positivity for vimentin and CD34 and negativity for factor XIIIa staining. Apolipoprotein has also been described as a marker for DFSP.

Preferred treatment for DFSP is wide surgical excision with pathologically negative margins. Recently Imatinib mesylate therapy has been documented to induce extensive regression of primary and metastatic lesions.

Despite the local invasiveness, DFSP rarely metastasizes. The risk for development of metastatic disease is only 5%. The extent of surgical excision determines the prognosis of the patient. To reduce the local recurrence rate, a wide surgical excision with adequate margins is used.

Cytogenetically, DFSP is characterized by the presence of the recurrent t(17;22)(q22;q13) translocation or, more commonly, supernumerary ring chromosomes containing material from chromosomal regions 17q22 and 22q13 accompanied by simple chromosome trisomies. The translocation results in the fusion of the alpha chain type 1 of collagen (COL1A1) gene with the platelet-derived growth factor Beta (PDGFbeta) gene.

Fluorescence in situ hybridization based approaches can be used to demonstrate the t(17;22), using gene specific probes to demonstrate PDGFbeta gene rearrangements as well as genetic gains and losses.

COL1A1 (collagen, type I, alpha 1)

17q21.33

Molecular Location: From base pairs 45,616,456 to 45,633,999.

COL1A1 is transcribed from centromere to telomere at 17q21.31-q22. The mRNA sequence contains 5927bp, comprising 52 exons and spans approximately 18kb. Exons 5 to 49 encode the alpha helical domain.

The COL1A1 gene produces a component of type I collagen called the pro-a1(I) chain. The Alpha1 (I) chains of the type I collagen are synthesized as procollagen molecules containing amino and carboxy-terminal propeptides, which are removed by site-specific endopeptidase synthesizing the 1464 amino acid protein.

PDGFB platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog)

22q13.1

Molecular Location: From base pairs 37,949,665 to 37,970,936.

The PDGFbeta mRNA sequence contains 3373bp, comprising 7 exons and spans approximately 22kb. Exon 7 and most part of the exon 1 are non-coding sequences.

The PDGFbeta chains are synthesized as 240 amino acids precursors molecules containing amino and carboxy-terminal propeptides, which are removed by site-specific endopeptidases. Two PDGFbeta precursor chains associate in dimers to form the mature PDGFBB after proteolysis.

COL1A1 and PDGFbeta both encoded as pro-peptides are processed by proteolytic cleavage at N and C-terminus to give mature proteins. Sequences analyses of the chimerical COL1A1/PDGFbeta fusion transcripts has shown that the COL1A1/PDGFbeta putative proteins exhibit a pro-peptide structure, with a preserved N-terminus COL1A1 pro-peptide containing the signal peptide and the N and C-terminus PDGFbeta maturation cleavage sites. The result of this characteristic rearrangement of COL1A1and PDGFbeta is the transcriptional up-regulation of the PDGFB gene. The associated COL1A1-PDGFbeta fusion protein is posttranslationally processed to a functional PDGFbeta and results in PDGFbeta-mediated autocrine and/or paracrine activation of platelet-derived growth factor receptor-beta (PDGFBB).