title: Coexpression of NOR1 and SIX3 proteins in extraskeletal myxoid chondrosarcomas without detectable NR4A3 fusion genes.
abstract: Extraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal tumor cytogenetically characterized by reciprocal translocations, such as t(9;22)(q22;q12) and t(9;17)(q22;q11), which result in EWSR1/NR4A3 and TAF15/NR4A3 fusion genes (alias EWS/NOR1, TAF2N/NOR1), respectively. NOR1 is an orphan nuclear receptor and acts as a transcription factor that can bind to its putative coactivator, SIX3. Although the NOR1 fusion protein has been implicated in oncogenesis of EMC, a small fraction of EMC lacks detectable rearrangements of the NR4A3 gene or 9q22. We report a case of EMC with no detectable NR4A3 gene alterations, as assessed with various molecular techniques including reverse transcription-polymerase chain reaction (RT-PCR), Southern blotting, interphase fluorescence in situ hybridization, and PCR single-strand conformation polymorphism-but with coexpression of native NOR1 and SIX3. In our survey of another 18 EMCs, we identified one more case expressing both NOR1 and SIX3 but lacking NR4A3 fusion. Fourteen tumors with detectable NR4A3 fusion genes (EWSR1-NR4A3; TAF15-NR4A3) expressed neither native NOR1 nor SIX3. SIX3 expression is normally confined specifically to the developing eye and fetal forebrain, although the expression of NR4A3 is largely ubiquitous. Our data suggest that aberrant coexpression of NOR1 and SIX3 is a potential alternative mechanism underlying the development of EMC.
authors.affiliation: Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hisaoka
authors.forename: Sumika
authors.initials: S
authors.lastname: Okamoto
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
mesh_terms: D000368:Aged; D015139:Blotting, Southern; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002813:Chondrosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D008297:Male; D026901:Membrane Transport Proteins; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097607:Homeobox Protein SIX3
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015514:Oncogene Proteins, Fusion; D011506:Proteins; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D000097607:Homeobox Protein SIX3; C490412:NR4A3 protein, human; C479458:OSCP1 protein, human