title: Molecular characterization of the MLL-SEPT6 fusion gene in acute myeloid leukemia: identification of novel fusion transcripts and cloning of genomic breakpoint junctions.
abstract: One of the MLL fusion partners in leukemia is the SEPT6 gene, which belongs to the evolutionarily conserved family of genes of septins. In this work we aimed to characterize at both the RNA and DNA levels three acute myeloid leukemias with cytogenetic evidence of a rearrangement between 11q23 and Xq24. Molecular analysis led to the identification of several MLL-SEPT6 fusion transcripts in all cases, including a novel MLL-SEPT6 rearrangement (MLL exon 6 fused with SEPT6 exon 2). Genomic DNA breakpoints were found inside or near Alu or LINE repeats in the MLL breakpoint cluster region, whereas the breakpoint junctions in the SEPT6 intron 1 mapped to the vicinity of GC-rich low-complexity repeats, Alu repeats, and a topoisomerase II consensus cleavage site. These data suggest that a non-homologous end-joining repair mechanism may be involved in the generation of MLL-SEPT6 rearrangements in acute myeloid leukemia.
authors.affiliation: Department of Genetics, Portuguese Oncology Institute, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Cerveira
authors.forename: Francesca
authors.initials: F
authors.lastname: Micci
authors.forename: Joana
authors.initials: J
authors.lastname: Santos
authors.forename: Manuela
authors.initials: M
authors.lastname: Pinheiro
authors.forename: Cecília
authors.initials: C
authors.lastname: Correia
authors.forename: Susana
authors.initials: S
authors.lastname: Lisboa
authors.forename: Susana
authors.initials: S
authors.lastname: Bizarro
authors.forename: Lucília
authors.initials: L
authors.lastname: Norton
authors.forename: Anders
authors.initials: A
authors.lastname: Glomstein
authors.forename: Ann E
authors.initials: AE
authors.lastname: Asberg
authors.forename: Sverre
authors.initials: S
authors.lastname: Heim
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D003001:Cloning, Molecular; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*
chemical_list: C512503:MLL-SEPT6 fusion protein, human; D015514:Oncogene Proteins, Fusion