title: Several fusion genes identified by whole transcriptome sequencing in a spindle cell sarcoma with rearrangements of chromosome arm 12q and MDM2 amplification.
abstract: Spindle cell tumors are clinically heterogeneous but morphologically similar neoplasms that can occur anywhere, mostly in adult patients. They are treated primarily with surgery to which is often added adjuvant or neoadjuvant radiation. Sub-classification of spindle cell sarcomas requires integration of histology, clinicopathological parameters, immunohistochemistry, cytogenetics (including fluorescence in situ hybridization) and/or molecular genetics. Some of the tumor subtypes are characterized by the presence of distinct chromosomal translocations and fusion genes. When no signs of differentiation are seen, the diagnosis by exclusion becomes undifferentiated spindle cell sarcoma. Cytogenetic, RNA sequencing and RT-PCR analyses were performed on a case of spindle cell sarcoma. The karyotype of the primary tumor was 46,X,del(X)(p?11p?22), der(12)(12pter→12q?22::12q?15→q?22::16p11→16pter),-16,+r(12). MDM2 was found amplified in both the primary tumor and a meta-stasis. RNA-Seq of the primary tumor identified four fusion genes, PTGES3-PTPRB, HMGA2-DYRK2, TMBIM4-MSRB3 and USP15-CNTN1, in which all the partner genes map to the q arm of chromosome 12. In material from the metastasis, RT-PCR detected the PTGES3-PTPRB, HMGA2-DYRK2 and TMBIM4-MSRB3 whereas no USP15-CNTN1 fusion transcript was found. Because MDM2 amplification and the fusion transcripts PTGES3-PTPRB, HMGA2-DYRK2 and TMBIM4-MSRB3 were found both in the primary tumor and in the metastasis, they are components of the same clone and may be involved both in initiation and progression of the tumor. Which of them is pathogenetically primary remains unknown.
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Bodil
authors.initials: B
authors.lastname: Bjerkehagen
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Gorunova
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Berner
authors.affiliation: Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Boye
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Sverre
authors.initials: S
authors.lastname: Heim
mesh_terms: D000328:Adult; D063646:Carcinogenesis; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D025743:HMGA2 Protein / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007621:Karyotyping; D009362:Neoplasm Metastasis; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000302:isolation & purification; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D025743:HMGA2 Protein; D015514:Oncogene Proteins, Fusion; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2