Abstract for presentation at 11th International Congress of Human Genetics

Molecular cytogenetic strategy for the early detection and characterization of Fanconi Anemia-specific MDS- and AML-associated chromosomal imbalances

  • Dr Holger Tonnies, Institute of Human Genetics, Charité, Universitaetsmedizin Berlin, Berlin, Germany
  • Antje Gerlach, Institute of Human Genetics, Charité, Universitaetsmedizin Berlin, Berlin, Germany
  • Reyk Richter, Institute of Human Genetics, Charité, Universitaetsmedizin Berlin, Berlin, Germany
  • Prof Dr Heidemarie Neitzel, Institute of Human Genetics, Charité, Universitaetsmedizin Berlin, Berlin, Germany

    • Purpose: Bone marrow (BM) failure in Fanconi Anemia (FA) patients followed by myelodysplastic syndrome or AML is strongly associated with the occurrence of FA-specific clonal chromosomal imbalances in BM cells. Specific chromosomal imbalances are strongly associated with a poor prognosis and represent an adverse risk factor in FA for the progression into MDS/AML, and also for recurrent severe infections (Tönnies et al. 2003, Blood). Additionally, our studies showed, that the adverse clones can appear and expand very fast in vivo. We therefore established and validated additional to conventional karyotyping a comparative genomic hybridization (CGH) and interphase fluorescence in situ hybridization (I-FISH) based strategy for the early detection of adverse clonal chromosomal imbalances in uncultivated BM and peripheral blood (PB) cells from FA patients.
    Methods: As whole metaphase and whole genome screening methods, conventional karyotyping (BM) and comparative genomic hybridization (BM- and PB-DNA) were used. Collected data on chromosomal imbalances have been directly integrated in an I-FISH probe set for the early, sensitive, and automated high-throughput detection of adverse clones in FA-BM and PB cells.
    Results: By performing more than 400 analyses on material from FA patients, specific unbalanced translocations in bone marrow cells have been detected, validated and followed up using I-FISH.
    Conclusions: By using this strategy we were able to detect adverse clones fast, sensitively, and early (in PB cells without bone marrow aspiration). We integrated an I-FISH scanning system which allows a stable, evaluator-variation free high-speed detection and quantification of aberrant clones in BM and PB cells of FA patients. Furthermore, subpopulations of interphase cells from PB direct preparations (e.g. granulocytes), reflecting the in vivo quantity of aberrant clones, can be evaluated selectively without former enrichment of these cells.

    Conference Organiser - ICMS Pty Ltd