title: Characterization of a recurrent t(1;2)(p36;p24) in human uterine leiomyoma.
abstract: Uterine leiomyomas are the most common neoplasms in women of reproductive age. Approximately 40% of these neoplasms show recurring structural cytogenetic anomalies, including del(7)(q22), t(12;14)(q15;q24), t(1;2)(p36;p24), and anomalies affecting 6p21 or 10q22. Using positional cloning strategies, we and others had previously identified HMGA1, HMGA2, RAD51L1, and MYST4 (previously referred to as MORF); as primary target (fusion) genes associated with tumor development in three of these distinct cytogenetic subgroups. Here, we report the positional cloning of a single, recurrent, leiomyoma-associated anomaly, t(1;2)(p36;p24). Molecular characterization of the reciprocal breakpoint intervals showed that that AJAP1 (alias SHREW1) and NPHP4 flank the breakpoint on chromosome 1 and that ITSN2 and NCOA1 flank the breakpoint on chromosome 2. Detailed analysis of the breakpoint regions revealed that in this particular case the translocation was associated with a 27-bp deletion on chromosome 1 and a 136-bp duplication on chromosome 2. No breakpoint-spanning (fusion) genes were identified. In silico prediction of transcription factor binding sites, however, indicated the presence of several such sites in the respective breakpoint regions, and major changes therein as a result of the t(1;2)(p36;p24) under investigation. We postulate that transcriptional deregulation of one or more of these breakpoint-flanking genes may contribute to the development of human uterine leiomyomas.
authors: Department of Human Genetics, Radboud University Nijmegen Medical Center, and Nijmegen Center for Molecular Life Sciences, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors: Anke
authors: A
authors: van Rijk
authors: Marcel
authors: M
authors: Sweers
authors: Erik
authors: E
authors: Huys
authors: Monique
authors: M
authors: Kersten
authors: Gerard
authors: G
authors: Merkx
authors: Ad Geurts
authors: AG
authors: van Kessel
authors: Maria
authors: M
authors: Debiec-Rychter
authors: Eric F P M
authors: EF
authors: Schoenmakers
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003001:Cloning, Molecular; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D007621:Karyotyping; D007889:Leiomyoma / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014178:Translocation, Genetic; D014594:Uterine Neoplasms / Q000235:genetics*
chemical_list: D014157:Transcription Factors