title: Genomic imbalances are confined to non-proliferating cells in paediatric patients with acute myeloid leukaemia and a normal or incomplete karyotype.
abstract: Leukaemia is often associated with genetic alterations such as translocations, amplifications and deletions, and recurrent chromosome abnormalities are used as markers of diagnostic and prognostic relevance. However, a proportion of acute myeloid leukaemia (AML) cases have an apparently normal karyotype despite comprehensive cytogenetic analysis. Based on conventional cytogenetic analysis of banded chromosomes, we selected a series of 23 paediatric patients with acute myeloid leukaemia and performed whole genome array comparative genome hybridization (aCGH) using DNA samples derived from the same patients. Imbalances involving large chromosomal regions or entire chromosomes were detected by aCGH in seven of the patients studied. Results were validated by fluorescence in situ hybridization (FISH) to both interphase nuclei and metaphase chromosomes using appropriate bacterial artificial chromosome (BAC) probes. The majority of these copy number alterations (CNAs) were confirmed by FISH and found to localize to the interphase rather than metaphase nuclei. Furthermore, the proliferative states of the cells analyzed by FISH were tested by immunofluorescence using an antibody against the proliferation marker pKi67. Interestingly, these experiments showed that, in the vast majority of cases, the changes appeared to be confined to interphase nuclei in a non-proliferative status.
authors.affiliation: Centre for Cell and Chromosome Biology and Brunel Institute of Cancer Genetics and Pharmacogenomics, Division of Biosciences, Brunel University, West London, United Kingdom.
authors.forename: Erica
authors.initials: E
authors.lastname: Ballabio
authors.forename: Regina
authors.initials: R
authors.lastname: Regan
authors.forename: Elisa
authors.initials: E
authors.lastname: Garimberti
authors.forename: Jochen
authors.initials: J
authors.lastname: Harbott
authors.forename: Jutta
authors.initials: J
authors.lastname: Bradtke
authors.forename: Andrea
authors.initials: A
authors.lastname: Teigler-Schlegel
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cazzaniga
authors.forename: Giovanni
authors.initials: G
authors.lastname: Giudici
authors.forename: James S
authors.initials: JS
authors.lastname: Wainscoat
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Boultwood
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Bridger
authors.forename: Samantha J L
authors.initials: SJ
authors.lastname: Knight
authors.forename: Sabrina
authors.initials: S
authors.lastname: Tosi
mesh_terms: D000328:Adult; D002467:Cell Nucleus / Q000235:genetics; D049109:Cell Proliferation; D002648:Child; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D008297:Male; D015203:Reproducibility of Results