title: Cytogenetic and molecular heterogeneity of 7q36/12p13 rearrangements in childhood AML.
abstract: The t(7;12)(q36;p13) is a recurrent abnormality in acute myeloid leukemia (AML) of childhood. The involved gene on chromosome 12 is TEL; the 7q36 partner gene has not been identified. We describe morphologic, molecular and cytogenetic characterization of two cases of 7q36/12p13-associated AML that provide important insights regarding the consequences of this rearrangement. First, the molecular organization of the breakpoint regions differ significantly: one case is a reciprocal 7;12 translocation (RTR); the other has an insertion of 7q into 12p (INS). While 12p13 breakpoints in both patients interrupt TEL intron 1, the centromere to telomere orientation of the 7q36 sequences relative to the TEL sequences are inverted in INS compared to RTR. This difference makes it difficult to postulate a mechanism whereby both patients could produce a common fusion transcript. Further, no evidence was obtained for any TEL-containing fusion transcripts. Finally, we report the first cloning of a 7;12 genomic breakpoint (from RTR) and find that it maps to a site 30 kbp proximal to the HLXB9 gene in 7q36. Together, these data suggest that, unlike most leukemia-associated chromosomal rearrangements, the important consequence of the t(7;12) is likely not the generation of a novel fusion transcript, but instead the inactivation of TEL and/or a gene at 7q36.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Simmons
authors.forename: L
authors.initials: L
authors.lastname: Oseth
authors.forename: P
authors.initials: P
authors.lastname: Nguyen
authors.forename: M
authors.initials: M
authors.lastname: O'Leary
authors.forename: K F
authors.initials: KF
authors.lastname: Conklin
authors.forename: B
authors.initials: B
authors.lastname: Hirsch
mesh_terms: D001483:Base Sequence; D019457:Chromosome Breakage; D002881:Chromosomes, Human, Pair 12; D002897:Chromosomes, Human, Pair 7; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D015321:Gene Rearrangement; D018740:Genetic Heterogeneity; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins / Q000235:genetics; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein