CENTROMERIC INSTABILITY OF CHROMOSOME-1 RESULTING IN MULTIBRANCHED CHROMOSOMES, TELOMERIC FUSIONS, AND JUMPING TRANSLOCATIONS OF 1Q IN A HUMAN IMMUNODEFICIENCY VIRUS-RELATED NON-HODGKINS-LYMPHOMA

Background. Acquired immunodeficiency syndrome-related non-Hodgkin's l ymphomas are associated with the B-cell chromosomal translocation t(8; 14)(q24; q32). The most common secondary chromosome aberrations in the se patients involve 1q and are believed to be associated with tumor pr ogression. A mechanism for the origin of these Iq aberrations has not been demonstrated. To their knowledge, the authors report the first hu man immunodeficiency virus (HIV)-positive patient to have centromeric decondensation and multibranched chromosome aberrations of chromosomes 1 and 16 resulting in telomeric associations and ''jumping translocat ions'' of 1q. Methods. Tumor cells from peritoneal fluid of an HIV-pos itive patient were cultured for 24, 48, and 72 hours and analyzed by b oth conventional G-banding and fluorescence in situ hybridization. Res ults. G-band analysis showed a stemline with t(8;14)(q24;q32), but als o showed the progression from centromeric decondensation to multibranc hed chromosome configurations of chromosomes 1 and 16. The interchange and duplications of chromosome arms resulted in the gain of extra cop ies of Iq material on a number of different chromosomes, but also the loss of 16q in at least one sideline and the formation of micronuclei. Fluorescence in situ hybridization analysis demonstrated that micronu clei predominantly involved chromosome 1 and, to a lesser extent, chro mosome 16. Conclusions. The cytogenetic findings in this unique case s uggest that immunodeficiency may be a factor involved in centromeric i nstability, multibranching, and the progression to the subsequent form ation of telomeric fusions and multiple unbalanced translocations of 1 q (jumping translocations). The striking similarity of the centromeric instability in this patient to those with ICF syndrome (variable immu nodeficiency, centromeric heterochromatin instability, and facial anom alies) suggests hypomethylation as the etiologic mechanism for the chr omosome instability.