Molecular characterization of the MLL-SEPT6 fusion gene in acute myeloid leukemia: identification of novel fusion transcripts and cloning of genomic breakpoint junctions.
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.
Cerveira
Nuno
N
Department of Genetics, Portuguese Oncology Institute, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
Micci
Francesca
F
Santos
Joana
J
Pinheiro
Manuela
M
Correia
Cecília
C
Lisboa
Susana
S
Bizarro
Susana
S
Norton
Lucília
L
Glomstein
Anders
A
Asberg
Ann E
AE
Heim
Sverre
S
Teixeira
Manuel R
MR
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*
C512503:MLL-SEPT6 fusion protein, human; D015514:Oncogene Proteins, Fusion