Disease-specific gene repositioning in breast cancer

The nuclear repositioning of specific genes may be a novel diagnostic strategy to distinguish malignant from normal tissue

Spatial Association of Homologous Pericentric Regions in Human Lymphocyte Nuclei during Repair

Spatial positioning of pericentric chromosome regions in human lymphocyte cell nuclei was investigated during repair after H(2)O(2)/L-histidine treatment. Fifteen to three-hundred minutes after treatment, these regions of chromosomes 1, 15, and X were labeled by fluorescence in situ hybridization. The relative locus distances (LL-distances), the relative distances to the nuclear center (LC-distances), and the locus-nuclear center-locus angles (LCL-angles) were measured in ∼5000 nuclei after two-dimensional microscopy. Experimental frequency histograms were compared to control data from untreated stimulated and quiescent (G(0)) nuclei and to a theoretical two-dimensional projection from random points. Based on the frequency distributions of the LL-distances and the LCL-angles, an increase of closely associated labeled regions was found shortly after repair activation. For longer repair times this effect decreased. After 300 min the frequency distribution of the LL-distances was found to be compatible with the random distance distribution again. The LL-distance frequency histograms for quiescent nuclei did not significantly differ from the theoretical random distribution, although this was the case for the stimulated control of chromosomes 15 and X. It may be inferred that, concerning the distances, homologous pericentric regions appear not to be randomly distributed during S-phase, and are subjected to dynamic processes during replication and repair

Paediatric acute myeloid leukaemia with the t(7;12)(q36;p13) rearrangement: a review of the biological and clinical management aspects

The presence of chromosomal abnormalities is one of the most important criteria for leukaemia diagnosis and management. Infant leukaemia is a rare disease that affects children in their first year of life. It has been estimated that approximately one third of infants with acute myeloid leukaemia harbour the t(7;12)(q36;p13) rearrangement in their leukaemic blasts. However, the WHO classification of acute myeloid leukaemia does not yet include the t(7;12) as a separate entity among the different genetic subtypes, although the presence of this chromosomal abnormality has been associated with an extremely poor clinical outcome. Currently, there is no consensus treatment for t(7;12) leukaemia patients. However, with the inferior outcome with the standard induction therapy, stem cell transplantation may offer a better chance for disease control. A better insight into the chromosome biology of this entity might shed some light into the pathogenic mechanisms arising from this chromosomal translocation, that at present are not fully understood. Further work is needed to improve our understanding of the molecular and genetic basis of this disorder. This will hopefully open some grounds for possible tailored treatment for this subset of very young patients with inferior disease outcome. This review aims at highlighting the cytogenetic features that characterise the t(7;12) leukaemias for a better detection of the abnormality in the diagnostic setting. We also review treatment and clinical outcome in the cases reported to date