title: Fusion of the FUS and CREB3L2 genes in a supernumerary ring chromosome in low-grade fibromyxoid sarcoma.
abstract: Low-grade fibromyxoid sarcoma (LGFMS) is a rare, low-grade malignant soft tissue tumor that is often mistaken for either benign or more malignant tumor types. Commonly, this tumor affects young adults and typically arises in the deep proximal extremities or trunk with frequent recurrences and can metastasize to the lungs many years later. Most cases have a recurrent balanced translocation involving chromosomes 7 and 16, t(7;16)(q32-34;p11), which leads to the fusion of the FUS and CREB3L2 genes. However, supernumerary ring chromosomes have been identified in a subset of FUS/CREB3L2-positive LGFMS, but it has not yet been formally demonstrated that such ring chromosomes harbor the FUS/CREB3L2 fusion gene. Here, we report the genetic findings of a supernumerary ring chromosome from an LGFMS from a 77-year-old man. Chromosome banding analysis revealed a supernumerary ring chromosome, and further studies with fluorescence in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR) showed that the ring contained material from chromosomes 7 and 16, that the FUS gene was present in two rearranged copies, and that it expressed the FUS/CREB3L2 fusion gene. Moreover, an assessment of previously reported cases showed that tumors with ring chromosomes relapsed more often than tumors with a balanced t(7;16), suggesting that ring formation in LGFMS is correlated with tumor progression.
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, SE-221 85 Lund, Sweden. hammurabi.bartuma@med.lu.se
authors.forename: Hammurabi
authors.initials: H
authors.lastname: Bartuma
authors.forename: Emely
authors.initials: E
authors.lastname: Möller
authors.forename: Anna
authors.initials: A
authors.lastname: Collin
authors.forename: Henryk A
authors.initials: HA
authors.lastname: Domanski
authors.forename: Fredrik Vult
authors.initials: FV
authors.lastname: Von Steyern
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
mesh_terms: D000368:Aged; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005354:Fibrosarcoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D012303:Ring Chromosomes; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C518609:CREB3L2 protein, human; D015514:Oncogene Proteins, Fusion; D034702:RNA-Binding Protein FUS