Identification of parental chromosomes involved in translocations BCR-ABL, t(9;22) and PML-RARA, t(15;17).

Cells of blood and bone marrow often exhibit a genome- or ploidywise organization of the two haploid sets, representing apparently maternal and paternal chromosomes in interphase nuclei and in metaphase spreads.This provide s the opportunity to perform "genomic karyotyping." Such application of karyotyping may indicate whether two chromosomes involved in a translocation are both maternal, both paternal, or intermingled, i.e. one maternal and the other paternal (we refer to this as mixed). The parental origin for these translocations likely has profound differences and implications in disease expression and response to treatments, making such information very important to personalized medicine. In this mini-review, we present our observations from specimens with translocations BCR-ABL, t(9;22) and PML-RARA, t(15;17).About 20% metaphases of these specimens indicated ploidywise organization and were amenable to genomic karyotyping analysis. Fluorescence in situ hybridization (FISH) probes for BCR-ABL translocation suggest a close approximation of the HSA 9 and 22, as control values for false-positive signals run from approximately 5-10%. Given a ploidywise distribution of the maternal and paternal sets of chromosomes, it would be expected that the chromosomes involved in the translocation t(9;22) would more often belong to one of the two genomes, either maternal or paternal. Contrastingly, HSA 15 and 17 are not considered as spatially close to each other and therefore an intragenomic involvement would be rarer for translocation t(15;17). In 14 out of the 21 (66.6%) specimens with informative metaphases, the chromosomes involved in the translocation BCR-ABL were restricted to one of the two genomes - either maternal or paternal. In cases of translocation PML-RARA only 4 out of 21 (19.1%) specimens indicated an intragenomic involvement. These simple yet informative analyses of cancer-related translocations show profound underlying genomic origins and lend support to genomic karyotyping. Although Giemsa banding provides a means for the identification of individual human chromosomes, determining the spatial position and orientation of these chromosomes within the nucleus remains elusive. DNA distribution studies of blood and bone marrow cells using image cytometry yielded results suggesting a ploidywise intranuclear order, later supported by chromosome specific fluorescence in situ hybridization ((unpublished observations, J. P. Chaudhuri and G. Burger (1)). On the basis of these observations, the concept of genomic karyotyping has been postulated (2, 3). Here, a comparative study of chromosomal translocations is described indicating evidence of this order in metaphase cells and its implications in diagnosis and therapy.