title: Microhomologies and interspersed repeat elements at genomic breakpoints in chronic myeloid leukemia.
abstract: Reciprocal translocation t(9;22) is central to the pathogenesis of chronic myeloid leukemia. Some authors have suggested that Alu repeats facilitate this process, but supporting analyses have been sparse and often anecdotal. The purpose of this study was to analyze the local structure of t(9;22) translocations and assess the relevance of interspersed repeat elements at breakpoints. Collected data have been further compared with the current models of DNA recombination, in particular the single-strand annealing (SSA) and the nonhomologous end joining (NHEJ) processes. We developed a protocol for the rapid characterization of patient-specific genomic junctions and analyzed 27 patients diagnosed with chronic myeloid leukemia. Sequence analysis revealed microhomologies at the junctions of 21 patients of 27, while interspersed repeats were of relevance (P < 0.05) in at least 16 patients. These findings are more frequent than expected and give an indication that the main mechanisms involved in the t(9;22) translocation are the SSA and NHEJ pathways, both playing a role. Furthermore, our report is consistent with microhomologies facilitating the joining of DNA ends in the translocation process, and with both Alu and a variety of other repeat sequences pairing nonhomologous chromosomes during the SSA pathway.
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, Università dell'Insubria, Varese, Italy. elia.mattarucchi@uninsubria.it
authors.forename: Elia
authors.initials: E
authors.lastname: Mattarucchi
authors.forename: Vittoria
authors.initials: V
authors.lastname: Guerini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Campiotti
authors.forename: Achille
authors.initials: A
authors.lastname: Venco
authors.forename: Francesco
authors.initials: F
authors.lastname: Pasquali
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo Curto
authors.forename: Giovanni
authors.initials: G
authors.lastname: Porta
mesh_terms: D001483:Base Sequence; D019457:Chromosome Breakage; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D015331:Cohort Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D020071:Interspersed Repetitive Sequences / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D016044:Fusion Proteins, bcr-abl