title: Cytogenetic and molecular characterization of double inversion 3 associated with a cryptic BCR-ABL1 rearrangement and additional genetic changes.
abstract: Rearrangements of chromosome 3 involving bands 3q21 and 3q26 have been reported in about 2% of patients with acute myeloid leukemia, and rarely in myelodysplastic syndrome or chronic myelogenous leukemia (CML). To date, only six cases of inversion of both homologues have been reported. Loss of normal chromosome 3 and duplication of the inverted chromosome have been proposed as the most likely mechanism, but have not been shown experimentally. We present a 36-year-old male with an initial diagnosis of CML and resistance to imatinib mesylate. Chromosome analysis showed an inversion within the long arm of both homologues of chromosome 3 and an interstitial deletion within the long arm of one chromosome 7. The rearrangement of EVI1 locus on both homologues of chromosome 3 was confirmed by fluorescence in situ hybridization (FISH). Additional FISH studies showed a cryptic insertion of ABL1 into the BCR region, and subsequent duplication of the derivative chromosome 22. The single-nucleotide polymorphism array showed copy-neutral loss of heterozygosity on chromosomes 3 and 22, suggesting that a somatic repair mechanism is involved in the evolution of these genetic alterations. This case illustrates the complexity of genetic aberrations in neoplastic cells, and the value of array technology, used in concert with conventional cytogenetic methods, for a better understanding of the pathogenesis.
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, 84112, USA.
authors.forename: Reha
authors.initials: R
authors.lastname: Toydemir
authors.forename: Leslie
authors.initials: L
authors.lastname: Rowe
authors.forename: Michele
authors.initials: M
authors.lastname: Hibbard
authors.forename: Mohamed
authors.initials: M
authors.lastname: Salama
authors.forename: Shashirekha
authors.initials: S
authors.lastname: Shetty
mesh_terms: D000328:Adult; D001549:Benzamides; D002869:Chromosome Aberrations; D007446:Chromosome Inversion; D002892:Chromosomes, Human, Pair 22; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D011743:Pyrimidines / Q000494:pharmacology
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl