title: Spectral karyotyping and fluorescence in situ hybridization detect novel chromosomal aberrations, a recurring involvement of chromosome 21 and amplification of the MYC oncogene in acute myeloid leukaemia M2.
abstract: Recurring chromosomal aberrations are of aetiological, diagnostic, prognostic and therapeutic importance in acute myeloid leukaemia (AML). However, aberrations are detected in only two thirds of AML cases at diagnosis and recurrent balanced translocations in only 50%. Spectral karyotyping (SKY) enables simultaneous visualization of all human chromosomes in different colours, facilitating the comprehensive evaluation of chromosomal abnormalities. Therefore, SKY was used to characterize 37 cases of newly diagnosed AML-M2, previously analysed using G-banding. In 15/23 patients it was possible to obtain metaphases from viably frozen cells; in 22 additional cases, fixed-cell suspensions were used. Of the 70 chromosomal aberrations identified by SKY, 30 aberrations were detected for the first time, 18 aberrations were redefined and 22 were confirmed. SKY detected two reciprocal translocations, t(X;3) and t(11;19). In five cases, eight structural aberrations resulted in partial gains of chromosome 21, six of which were undetected by G-banding. In 4/5 cases, these resulted in copy number increases for AML1. Amplification of MYC was detected in three cases. Using SKY and FISH, clonal aberrations were identified in 5/18 cases with a presumed normal karyotype; 3/5 aberrations were of known unfavourable prognostic significance. Karyotypes were entered into a custom-designed SKY database, which will be integrated with other cytogenetic and genomic databases.
authors.affiliation: Genetics Department, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD, USA. hilgenfe@mail.nih.gov
authors.forename: E
authors.initials: E
authors.lastname: Hilgenfeld
authors.forename: H
authors.initials: H
authors.lastname: Padilla-Nash
authors.forename: N
authors.initials: N
authors.lastname: McNeil
authors.forename: T
authors.initials: T
authors.lastname: Knutsen
authors.forename: C
authors.initials: C
authors.lastname: Montagna
authors.forename: J
authors.initials: J
authors.lastname: Tchinda
authors.forename: J
authors.initials: J
authors.lastname: Horst
authors.forename: W D
authors.initials: WD
authors.lastname: Ludwig
authors.forename: H
authors.initials: H
authors.lastname: Serve
authors.forename: T
authors.initials: T
authors.lastname: Büchner
authors.forename: W E
authors.initials: WE
authors.lastname: Berdel
authors.forename: E
authors.initials: E
authors.lastname: Schröck
authors.forename: T
authors.initials: T
authors.lastname: Ried
mesh_terms: D002869:Chromosome Aberrations / Q000235:genetics*; D002871:Chromosome Banding; D025063:Chromosome Disorders; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D016208:Databases, Factual; D005260:Female; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping / Q000379:methods; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D012189:Retrospective Studies; D012815:Signal Processing, Computer-Assisted; D014178:Translocation, Genetic