title: Identification and characterization of novel human transcripts embedded within HMGA2 in t(12;14)(q15;q24.1) uterine leiomyoma.
abstract: The high mobility group A2 protein (HMGA2) has been implicated in the pathogenesis of mesenchymal tumors such as leiomyoma, lipoma and hamartoma. HMGA2 was pinpointed by mapping the breakpoints in the chromosomal translocations in 12q15, especially the t(12;14) that is commonly seen in uterine leiomyoma. It is generally assumed that altered expression of HMGA2 is an early event in the pathway to tumor formation. Here, we show evidence that three novel transcripts, A15, B6 and D12 are located within the HMGA2 gene itself and are transcribed from the opposite strand. These embedded transcripts are expressed at 6-20-fold higher levels in tumors compared to matched myometrium from the same patients. We estimate that the domain of increased expression extends 500kb on chromosome 12q15, and encompasses the majority of t(12;14) translocation breakpoints. However, a corresponding domain of consistently altered expression is not seen on chromosome 14 or outside of the chromosome 12 multiple aberration region. These data suggest that t(12;14) breakpoints contribute to the pathogenesis of uterine leiomyoma by interrupting a complex regulation of HMGA2 and other genes embedded within and around it. We also discovered a novel laminin receptor gene, transcribed from the opposite strand, within the promoter region of HMGA2. Although the roles for these embedded transcripts are still unknown, preliminary data suggest that they are members of the family of non-coding RNA and that they may play an important role in the pathology of uterine leiomyoma.
authors.affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, OH 45267-0524, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ingraham
authors.forename: Roy A
authors.initials: RA
authors.lastname: Lynch
authors.forename: Urvashi
authors.initials: U
authors.lastname: Surti
authors.forename: Joni L
authors.initials: JL
authors.lastname: Rutter
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Buckler
authors.forename: Sohaib A
authors.initials: SA
authors.lastname: Khan
authors.forename: Anil G
authors.initials: AG
authors.lastname: Menon
authors.forename: Pierig
authors.initials: P
authors.lastname: Lepont
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002881:Chromosomes, Human, Pair 12; D002883:Chromosomes, Human, Pair 14; D020224:Expressed Sequence Tags; D005260:Female; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007889:Leiomyoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009215:Myometrium / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017474:Receptors, Laminin / Q000235:genetics; D014178:Translocation, Genetic; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D025743:HMGA2 Protein; D017474:Receptors, Laminin