COL1A1-PDGFB Fusion Transcripts in Fibrosarcomatous Areas of Six Dermatofibrosarcomas Protuberans

Abstract

The fibrosarcomatous transformation of dermatofibrosarcoma protuberans (DFSP) has been considered for some time to be associated with an adverse clinical outcome. However, the molecular and cellular mechanism underlying the tumor progression remains undetermined. As the chimeric gene, COL1A1-PDGFB, has been proposed to play an important role in the histogenesis of DFSP, we conducted a reverse transcription-polymerase chain reaction assay to ascertain whether the COL1A1-PDGFB fusion transcripts can be detected in both conventional DFSP and fibrosarcomatous components of DFSP with fibrosarcomatous areas (DFSP-FS), using a simple method of microdissection on sections of archival formalin-fixed, paraffin-embedded tumor specimens from six DFSP-FS cases. The COL1A1-PDGFB fusion transcripts could be detected in FS areas in five of the six cases, whereas conventional DFSP areas of all cases expressed the chimeric mRNA. A subsequent sequence analysis of the polymerase chain reaction products confirmed that the detected messages were derived from identical gene fusions in the two different components of each of the five cases. Our results verify that the COL1A1-PDGFB fusion transcripts are preserved in the FS areas of most DFSP-FSs. The expression of the fusion transcripts in both conventional DFSP and FS areas of DFSP-FS supports a common histogenesis of the two components.

Identification of t(17;22)(q22;q13) (COL1A1/PDGFB) in dermatofibrosarcoma protuberans by fluorescence in situ hybridization in paraffin-embedded tissue microarrays

“…The authors attributed these results to the limited number of cases studied; they also accepted that other genetic alterations may be responsible for the progression of DFSP. The presence of a differential genetic profile in fibrosarcomatous transformation areas has also been studied by RT-PCR in a series of 6 DFSP-FS [30]. The COLA1-PDGFB transcripts could be detected in fibrosarcomatous areas in 5 of the 6 cases, whereas in conventional DFSP areas, all cases expressed the chimeric RNA [30].…”

Aberrant MAD2 expression in soft‐tissue sarcoma

“…Tumor type-specific fusion genes were detected using reverse transcription-polymerase chain reaction with formalin-fixed, paraffin-embedded tumor tissue specimens as previously described. [10][11][12][13][14] Four mm-thick sections of the formalin-fixed, paraffinembedded tumor tissue specimens were subjected to immunohistochemistry for MAD2 using a labeled polymeric secondary antibody (EnVision, DakoCytomation, Tokyo, Japan). After standard antigen retrieval in a pressure cooker for 10 min, an affinity purified anti-MAD2 rabbit antibody (Bethyl Laboratories, Montgomery, TX, USA, 1:500 dilution) was applied to the sections and incubated for 30 min at room temperature, followed by the application of diaminobenzidine and counterstaining with hematoxylin.…”

Gains of COL1A1-PDGFB genomic copies occur in fibrosarcomatous transformation of dermatofibrosarcoma protuberans

“…[9][10][11] Early case reports examining the cytogenetic alterations within fibrosarcomatous dermatofibrosarcoma protuberans indicate that the COL1A1-PDGFB fusion product is present in both fibrosarcomatous and dermatofibrosarcoma protuberans areas, indicating a common genetic origin for the two tumor components. 12 However, a single previous study was not able to find a difference in copy numbers between fibrosarcomatous and dermatofibrosarcoma protuberans areas using comparative genomic hybridization. 13 The objective of our study was to evaluate whether genomic gains of the COL1A1-PDGFB fusion gene occur during the clonal evolution of dermatofibrosarcoma protuberans into fibrosarcomatous dermatofibrosarcoma protuberans using fluorescence in situ hybridization.…”