title: Discovery of two novel EWSR1/ATF1 transcripts in four chimerical transcripts-expressing clear cell sarcoma and their quantitative evaluation.
abstract: The most common recurrent translocation in clear cell sarcoma t(12;22)(q13;q12) results in an EWSR1/ATF1 chimeric gene. We present a molecular analysis of tumor overgrowing right proximal tibia with bone destruction metastatic to two groin lymph nodes. Fluorescent in situ hybridization analysis performed on paraffin-embedded tissue sections of primary tumor sample indicated one rearranged locus of EWSR1 gene and one additional red signal. Reverse transcription-polymerase chain reaction analysis revealed the presence of four different EWSR1/ATF1 chimerical transcripts in the tumor sample as well as in both metastatic lymph nodes. Two previously described transcripts EWSR1exon7/ATF1exon5 and EWSR1exon8/ATF1exon4, and two novel transcripts EWSR1exon7/ATF1exon4 and EWSR1exon9/ATF1exon4 were identified. Both novel transcripts were out-of-frame fusions and, therefore, most likely had limited biological impact in oncogenesis of clear cell sarcoma. Quantitative evaluation demonstrated unequal distribution of these transcripts, with EWSR1exon8/ATF1exon4 type being overexpressed.
authors.affiliation: Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, Santariskiu 2, Vilnius LT-08661, Lithuania. arturas.jakubauskas@santa.lt
authors.forename: Arturas
authors.initials: A
authors.lastname: Jakubauskas
authors.forename: Vilma
authors.initials: V
authors.lastname: Valceckiene
authors.forename: Kristina
authors.initials: K
authors.lastname: Andrekute
authors.forename: Dmitrij
authors.initials: D
authors.lastname: Seinin
authors.forename: Arvydas
authors.initials: A
authors.lastname: Kanopka
authors.forename: Laimonas
authors.initials: L
authors.lastname: Griskevicius
mesh_terms: D051697:Activating Transcription Factor 1 / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D056905:Chromosome Breakpoints; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D019075:Electrophoresis, Capillary; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018227:Sarcoma, Clear Cell / Q000235:genetics* / Q000473:pathology; D013977:Tibia / Q000473:pathology
chemical_list: C531110:ATF1 protein, human; D051697:Activating Transcription Factor 1; D002148:Calmodulin-Binding Proteins; C500986:EWSR1 protein, human; D012333:RNA, Messenger; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins