title: HMGA2 is expressed in an allele-specific manner in human lipomas.
abstract: The architectural transcription factor HMGA2 is almost exclusively expressed in undifferentiated mesenchymal cells. Interestingly, it has been mapped to the translocation site in a variety of human mesenchymal tumors that reveal a terminally differentiated phenotype. The expression of chimeric HMGA2 transcripts encoding three DNA-binding domains fused to novel transcriptional regulatory domains was previously described in lipomas. In this study with lipoma ST91-198, we report the expression of truncated HMGA2 transcripts that gained no functional domains. The highly polymorphic region in the 5' untranslated region (UTR) of HMGA2 was used to determine the allele-specific expression of HMGA2 in lipomas. Microsatellite PCR revealed a monoallelic expression pattern, and only the translocated allele was expressed when the DNA-binding domains of the rearranged allele were fused with transcription activation domains. Surprisingly, a diallelic expression pattern of HMGA2 was observed in lipoma ST91-198, and the wild-type allele was also expressed. In conjunction with studies involving rearrangements of HMGA genes in other benign mesenchymal tumors, our results support a model in which the expression of the wild-type HMGA allele is critical for the pathogenesis of mesenchymal tumors and in which rearrangements of HMGA do not lead to a gain of function in the chimeric HMGA protein.
authors.affiliation: Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Hena R
authors.initials: HR
authors.lastname: Ashar
authors.forename: Alexei
authors.initials: A
authors.lastname: Tkachenko
authors.forename: Pritesh
authors.initials: P
authors.lastname: Shah
authors.forename: Kiran
authors.initials: K
authors.lastname: Chada
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008067:Lipoma / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D020121:5' Untranslated Regions; D025743:HMGA2 Protein