title: Extensive expression studies revealed a complex alternative splicing pattern of the HMGA2 gene.
abstract: Chromosomal rearrangements of the HMGA2 locus belong to the most common aberrations in human benign tumors. HMGA2 rearrangements often result in chimeric genes expressing transcripts consisting of the first three exons of HMGA2 followed by ectopic sequences derived from intron 3 of that gene. RT-PCR-based expression studies of 4 of these HMGA2 transcripts revealed a co-expression with the "wild-type" HMGA2a in tumor samples as well as in normal tissues. Northern blot hybridizations of the lipoma cell line Li-14 revealed the expression of five additional HMGA2 transcripts consisting of exons 1 to 3 but not exons 4 to 5 besides the full-length HMGA2a transcript. In silico analyses have been performed showing a high homology to well-established consensus sequences for the 3' splice acceptor site, the branch site, and poly(A) signal. Thus, it is quite obvious that the HMGA2 transcripts described herein are alternative, not aberrant, splice-products of the HMGA2 gene. It is hypothesized that HMGA2-dependent tumorigenesis is caused by a disturbed equilibrium in the co-expression of the HMGA2 splice variants leading to aberrant cell proliferation and/or malignant transformation of cells.
authors.affiliation: ZytoVision GmbH, Fischkai 1, D-27572 Bremerhaven, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hauke
authors.forename: Silke
authors.initials: S
authors.lastname: Leopold
authors.forename: Claudia
authors.initials: C
authors.lastname: Schlueter
authors.forename: Aljoscha M
authors.initials: AM
authors.lastname: Flohr
authors.forename: Hugo
authors.initials: H
authors.lastname: Murua Escobar
authors.forename: Piere
authors.initials: P
authors.lastname: Rogalla
authors.forename: Jörn
authors.initials: J
authors.lastname: Bullerdiek
mesh_terms: D017398:Alternative Splicing; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D002869:Chromosome Aberrations; D015972:Gene Expression Regulation, Neoplastic; D025765:HMGB3 Protein / Q000096:biosynthesis / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D040641:Quantitative Trait Loci / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics
chemical_list: D025765:HMGB3 Protein; D022821:RNA Splice Sites