title: The der(12)t(12;16) breakpoint in an acute leukaemia case targets a Sec7 domain containing protein.
abstract: A balanced translocation t(12;16)(p13;p13) in a patient with AML-M1 and bone marrow eosinophilia was previously analysed by FISH. The 16p13 breakpoint was shown to occur in the MYH11 gene, the fusion partner of CBFbeta in leukaemia patients with an inv(16) or a t(16;16), whereas the 12p13 breakpoint was shown to be present in cosmid c4H9. We present the molecular analysis of c4H9, resulting in the identification of a novel gene, SLAG. At the N-terminus, SLAG contains a Sec7 domain also found in proteins of the cytohesin family. In contrast to the cytohesins, no pleckstrin homology domain is present in SLAG. database searches identified several homologues, suggesting that SLAG defines a new subfamily of Sec7 proteins, characterised by an N-terminal Sec7 domain and a new C-terminal pleckstrin homology-like domain. The FISH data led to the hypothesis that rearrangement of SLAG might be involved in the pathogenesis of AML through the generation of a new fusion gene with MYH11. However, the putative SLAG-MYH11 fusions showed only weak transforming properties in NIH3T3 cells in a focus formation assay.
authors.affiliation: Human Genome Laboratory, Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium.
authors.forename: Anniek
authors.initials: A
authors.lastname: Corveleyn
authors.forename: Iwona
authors.initials: I
authors.lastname: Wlodarska
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
authors.forename: Peter
authors.initials: P
authors.lastname: Marynen
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D014178:Translocation, Genetic
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C502344:SLAG protein, human; C066755:Sec7 guanine nucleotide exchange factors