title: Fusion of the TBL1XR1 and HMGA1 genes in splenic hemangioma with t(3;6)(q26;p21).
abstract: RNA-sequencing of a splenic hemangioma with the karyotype 45~47,XX,t(3;6)(q26;p21) showed that this translocation generated a chimeric TBL1XR1-HMGA1 gene. This is the first time that this tumor has been subjected to genetic analysis, but the finding of an acquired clonal chromosome abnormality in cells cultured from the lesion and the presence of the TBL1XR1-HMGA1 fusion in them strongly favor the conclusion that splenic hemangiomas are of a neoplastic nature. Genomic PCR confirmed the presence of the TBL1XR1-HMGA1 fusion gene, and RT-PCR together with Sanger sequencing verified the presence of the fusion transcripts. The molecular consequences of the t(3;6) would be substantial. The cells carrying the translocation would retain only one functional copy of the wild-type TBL1XR1 gene while the other, rearranged allele could produce a putative truncated form of TBL1XR1 protein containing the LiSH and F-box-like domains. In the TBL1XR1-HMGA1 fusion transcript, furthermore, untranslated exons of HMGA1 are replaced by the first 5 exons of the TBL1XR1 gene. The result is that the entire coding region of HMGA1 comes under the control of the TBL1XR1 promoter, bringing about dysregulation of HMGA1. This is reminiscent of similar pathogenetic mechanisms involving high mobility genes in benign connective tissue tumors such as lipomas and leiomyomas.
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: 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: Bodil
authors.initials: B
authors.lastname: Bjerkehagen
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Ingvild
authors.initials: I
authors.lastname: Lobmaier
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; D002871:Chromosome Banding; D002893:Chromosomes, Human, Pair 3; D002896:Chromosomes, Human, Pair 6; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D025741:HMGA1a Protein / Q000235:genetics*; D006391:Hemangioma / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D013160:Splenic Neoplasms / Q000235:genetics*; D014178:Translocation, Genetic; D020506:Untranslated Regions
chemical_list: D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C473691:TBL1XR1 protein, human; D020506:Untranslated Regions; D025741:HMGA1a Protein