title: t(15;21) translocations leading to the concurrent downregulation of RUNX1 and its transcription factor partner genes SIN3A and TCF12 in myeloid disorders.
abstract: Through a combined approach integrating RNA-Seq, SNP-array, FISH and PCR techniques, we identified two novel t(15;21) translocations leading to the inactivation of RUNX1 and its partners SIN3A and TCF12. One is a complex t(15;21)(q24;q22), with both breakpoints mapped at the nucleotide level, joining RUNX1 to SIN3A and UBL7-AS1 in a patient with myelodysplasia. The other is a recurrent t(15;21)(q21;q22), juxtaposing RUNX1 and TCF12, with an opposite transcriptional orientation, in three myeloid leukemia cases. Since our transcriptome analysis indicated a significant number of differentially expressed genes associated with both translocations, we speculate an important pathogenetic role for these alterations involving RUNX1.
authors.affiliation: Department of Biology, University of Bari, Bari, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: L'Abbate
authors.affiliation: Department of Biology, University of Bari, Bari, Italy.
authors.forename: Doron
authors.initials: D
authors.lastname: Tolomeo
authors.affiliation: Department of Biology, University of Bari, Bari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Astis
authors.affiliation: Department of Biology, University of Bari, Bari, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Lonoce
authors.affiliation: UO Anatomia Patologica, Ospedale S. Martino, Belluno, Italy.
authors.forename: Crocifissa
authors.initials: C
authors.lastname: Lo Cunsolo
authors.affiliation: Unité de génétique du cancer, Service de génétique médicale, Centre Hospitalier Universitaire Vaudois CHUV, Lausanne, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Mühlematter
authors.affiliation: Unité de génétique du cancer, Service de génétique médicale, Centre Hospitalier Universitaire Vaudois CHUV, Lausanne, Switzerland.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schoumans
authors.affiliation: Center for Human Genetics and Department of Hematology, University Hospital Leuven and KU Leuven, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenberghe
authors.affiliation: Department of Haematology, AZ Sint-Jan AV, Brugge, Belgium.
authors.forename: Achilles
authors.initials: A
authors.lastname: Van Hoof
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Palumbo
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.affiliation: IRCCS Casa Sollievo della Sofferenza, Mendel Institute, San Giovanni Rotondo, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Mazza
authors.affiliation: Department of Biology, University of Bari, Bari, Italy. cleliatiziana.storlazzi@uniba.it.
authors.forename: Clelia Tiziana
authors.initials: CT
authors.lastname: Storlazzi
mesh_terms: D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014178:Translocation, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D012097:Repressor Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex; C493728:RUNX1 protein, human; C099683:SIN3A transcription factor; C073366:TCF12 protein, human