title: Identification of cytogenetic subclasses and recurring chromosomal aberrations in AML and MDS with complex karyotypes using M-FISH.
abstract: Complex chromosomal aberrations (CCAs) can be detected in a substantial proportion of AML and MDS patients, de novo as well as secondary or therapy-related, and are associated with an adverse prognosis. Comprehensive analysis of the chromosomal rearrangements in these complex karyotypes has been hampered by the limitations of conventional cytogenetics. As a result, our knowledge concerning the cytogenetics of these malignancies is sparse. Here we describe a multiplex-FISH (M-FISH) study of CCAs in 36 patients with AML and MDS. M-FISH generated a genome-wide analysis of chromosomal aberrations in CCAs, establishing several cytogenetic subgroups. -5/5q- was demonstrated in the majority of patients (86%). Other rearrangements (present with or without -5/5q-) included: deletion of 7q (47%), 3q rearrangements (19%), and MLL copy gain or amplification (17%). These genetic subgroups seem to display biological heterogeneity: MLL copy gain or amplification in association with 5q- was detected only in AML patients and was significantly associated with extremely short survival (median overall survival: 30 days, P = 0.0102). A partially cryptic t(4;5)(q31;q31), a balanced t(1;8)(p31;q22), and an unbalanced der(7)t(7;14)(q21;q13) were detected as possible new recurrent rearrangements in association with CCAs. Novel reciprocal translocations included t(5;11)(q33;p15)del(5)(q13q31) and t(3;6)(q26;q25). We conclude that AML and MDS with CCAs can be subdivided into molecular cytogenetic subclasses, which could reflect different clinical behavior and prognosis, and that three recurrent chromosomal aberrations are associated with karyotype complexity.
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Heidi
authors.initials: H
authors.lastname: Van Limbergen
authors.forename: Bruce
authors.initials: B
authors.lastname: Poppe
authors.forename: Lucienne
authors.initials: L
authors.lastname: Michaux
authors.forename: Christian
authors.initials: C
authors.lastname: Herens
authors.forename: Jill
authors.initials: J
authors.lastname: Brown
authors.forename: Luc
authors.initials: L
authors.lastname: Noens
authors.forename: Zwi
authors.initials: Z
authors.lastname: Berneman
authors.forename: Robrecht
authors.initials: R
authors.lastname: De Bock
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations / Q000145:classification*; D019457:Chromosome Breakage / Q000235:genetics; D002872:Chromosome Deletion; D020732:Cytogenetic Analysis / Q000379:methods*; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007621:Karyotyping / Q000379:methods; D007951:Leukemia, Myeloid / Q000145:classification* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000145:classification* / Q000235:genetics* / Q000401:mortality; D009693:Nucleic Acid Hybridization; D012189:Retrospective Studies; D016019:Survival Analysis; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D005819:Genetic Markers