title: Molecular detection of FUS-CREB3L2 fusion transcripts in low-grade fibromyxoid sarcoma using formalin-fixed, paraffin-embedded tissue specimens.
abstract: A diagnosis of low-grade fibromyxoid sarcoma (LGFMS) remains problematic because of its bland-looking histologic features that can be potentially confused with other benign or low-grade fibromyxoid lesions. Recent cytogenetic and molecular analyses have shown that most LGFMSs have a characteristic chromosomal abnormality, t(7;16)(q33;p11), resulting in the FUS-CREB3L2 fusion gene. However, such assays have only rarely been used to analyze formalin-fixed, paraffin-embedded tumor samples. In the present study, we conducted a reverse transcription-polymerase chain reaction assay to detect the FUS-CREB3L2 fusion transcripts using formalin-fixed, paraffin-embedded tumor tissue specimens from 16 LGFMSs including 3 cases with giant collagen rosettes. The primers were newly designed to specifically amplify most of the junctional regions of the FUS-CREB3L2 fusion gene transcripts previously reported. The FUS-CREB3L2 fusion gene transcripts were detected in 14/16 (88%) cases of LGFMS. A nucleotide sequence analysis of the PCR products revealed that different portions of the FUS exon 6 or 7 were fused with various sites of the CREB3L2 exon 5, resulting in 12 different nucleotide sequences. We also tested a primer set to detect the FUS-CREB3L1 fusion transcript, which is a rare variant of the gene fusion in LGFMS, although no PCR products were identified in any case. The FUS-CREB3L2 fusion transcripts were not detected in any of the 123 other soft-tissue tumors, including desmoid-type fibromatoses, myxofibrosarcomas, soft-tissue perineuriomas, and congenital or adult fibrosarcomas. These data suggest that our reverse transcription-polymerase chain reaction assay is a reliable method to detect FUS-CREB3L2, which can thus help in accurately diagnosing LGFMS.
authors.affiliation: Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Atsuji
authors.initials: A
authors.lastname: Matsuyama
authors.forename: Masanori
authors.initials: M
authors.lastname: Hisaoka
authors.forename: Shohei
authors.initials: S
authors.lastname: Shimajiri
authors.forename: Tomayoshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Imamura
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ishida
authors.forename: Masaharu
authors.initials: M
authors.lastname: Fukunaga
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukuhara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Minato
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Suguru
authors.initials: S
authors.lastname: Yonezawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuroda
authors.forename: Fumio
authors.initials: F
authors.lastname: Yamasaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Toyoshima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
mesh_terms: D000293:Adolescent; D000328:Adult; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics* / Q000473:pathology; D005557:Formaldehyde; D006652:Histological Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010232:Paraffin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: C485618:CREB3L1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D015514:Oncogene Proteins, Fusion; D005557:Formaldehyde; D010232:Paraffin