title: Non random distribution of genomic features in breakpoint regions involved in chronic myeloid leukemia cases with variant t(9;22) or additional chromosomal rearrangements.
abstract: BACKGROUND
  The t(9;22)(q34;q11), generating the Philadelphia (Ph) chromosome, is found in more than 90% of patients with chronic myeloid leukemia (CML). As a result of the translocation, the 3' portion of the ABL1 oncogene is transposed from 9q34 to the 5' portion of the BCR gene on chromosome 22 to form the BCR/ABL1 fusion gene. At diagnosis, in 5-10% of CML patients the Ph chromosome is derived from variant translocations other than the standard t(9;22).
  
  
  RESULTS
  We report a molecular cytogenetic study of 452 consecutive CML patients at diagnosis, that revealed 50 cases identifying three main subgroups: i) cases with variant chromosomal rearrangements other than the classic t(9;22)(q34;q11) (9.5%); ii) cases with cryptic insertions of ABL1 into BCR, or vice versa (1.3%); iii) cases bearing additional chromosomal rearrangements concomitant to the t(9;22) (1.1%). For each cytogenetic group, the mechanism at the basis of the rearrangement is discussed.All breakpoints on other chromosomes involved in variant t(9;22) and in additional rearrangements have been characterized for the first time by Fluorescence In Situ Hybridization (FISH) experiments and bioinformatic analyses. This study revealed a high content of Alu repeats, genes density, GC frequency, and miRNAs in the great majority of the analyzed breakpoints.
  
  
  CONCLUSIONS
  Taken together with literature data about CML with variant t(9;22), our findings identified several new cytogenetic breakpoints as hotspots for recombination, demonstrating that the involvement of chromosomes other than 9 and 22 is not a random event but could depend on specific genomic features. The presence of several genes and/or miRNAs at the identified breakpoints suggests their potential involvement in the CML pathogenesis.
authors.affiliation: Hematology, University of Bari, 70124 Bari, Italy. f.albano@ematba.uniba.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Albano
authors.forename: Luisa
authors.initials: L
authors.lastname: Anelli
authors.forename: Antonella
authors.initials: A
authors.lastname: Zagaria
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Coccaro
authors.forename: Paola
authors.initials: P
authors.lastname: Casieri
authors.forename: Antonella Russo
authors.initials: AR
authors.lastname: Rossi
authors.forename: Laura
authors.initials: L
authors.lastname: Vicari
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Liso
authors.forename: Mariano
authors.initials: M
authors.lastname: Rocchi
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D056905:Chromosome Breakpoints; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D000069439:Dasatinib; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D014178:Translocation, Genetic
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib