Robertsonian (15q;15q) translocation in a child with Angelman syndrome: Evidence of uniparental disomy

A balanced Robertsonian translocation 45,XY,t(15q15q) was detected in a patient with mental retardation, microcephaly, and hypertonia. Deletion of the 15q11q13 region was unlikely based on fluorescence in situ hybridization studies that revealed hybridization of appropriate DNA probes to both arms of the Robertsonian chromosome. Inheritance of alleles from 13 highly polymorphic DNA markers on chromosome 15 showed paternal uniparental isodisomy. The clinical, cytogenetic, and molecular results are consistent with a diagnosis of Angelman syndrome. © 1996 Wiley-Liss, Inc.     

Genetic effects of 1,2-dibromo-3-chloropropane (DBCP) in drosophila

Induction of sex-linked recessive lethal mutations, heritable translocations and genetic crossing-over were studied in Drosophila melanogaster males treated as adults and as embryos with different concentrations of gaseous DBCP. Adults exposed to 30 ppm/hr of the compound did not produce a significant number of sex-linked recessive lethal mutations in treated spermatozoa, spermatids, or spermato-cytes. However, at an exposure of 17.7 ppm/hr, a weak mutagenic effect was observed in embryonic spermatogonia. No translocation was scored in 4032 tested chromosomes from adults treated with 150 ppm/hr. However, a significant number of spermatocytial crossovers were induced after an exposure of 120 ppm/hr.     

Mechanism of chromosome exchange formation in human fibroblasts: Insights from “chromosome painting”

We have used the techniques of premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) with a library for human chromosome 4 to analyze the rate of rejoining of chromosome breaks and development of exchange aberrations in AG1522 human fibroblasts. AG1522 cells were irradiated in plateau phase with 10 Gy and fused with mitotic HeLa cells either immediately after irradiation or at intervals up to eight days later. The slides were then hybridized with the chromosome 4 library and unrejoined breaks and exchange events (visualized as bicolor chromosomes) scored in these cells. At the earliest time point after irradiation, the number of exchange events in the irradiated cells was low, but increased with kinetics similar to that of the joining of the breaks. Furthermore, when we analyzed those cells which had exchange events for their distribution, almost all of the cells initially contained one exchange event (1 bicolor chromosome). As time progressed, the number of cells containing exchanges with two exchange events per cell increased as the number with one exchange event per cell decreased. Extrapolation of the number of exchange events to zero time (with an estimate of 20 min for the fusion and condensation times) gave a value consistent with zero exchanges at zero time after irradiation. In a separate experiment, we also scored AG 1522 cells at the first metaphase after a dose of 6 Gy and were able to show that as many as 50% of the complete exchanges were non-reciprocal in nature, that is, the two broken ends of a single break in chromosome 4 joined to two different chromosomes. These data support the classical breakage-and-reunion model rather than the Revell Exchange Theory of exchange formation. © 1993 Wiley-Liss, Inc.     

Stem-Spermatogonial Survival and Incidence of Reciprocal Translocations in the γ-Irradiated Boar

To assess the effects of γ-radiation on stem-cell survival and incidence of reciprocal translocations, boar testes were irradiated with 100, 200, or 400 rad. Stem-cell survival was markedly affected by 100 rad (51 % of control) and reduced to 34% of control by 400 rad. Production of differentiating spermatogonia was all but completely interrupted by 200 rad and spermatogonial renewal was incomplete at 12 weeks. From the state of the seminiferous epithelium at 12 weeks, estimates of the percentage of permanent impairment of sperm-producing capacity ranged from 20 ± 6 (100 rad) to 67 ± 10 (400 rad). Incidence of translocations peaked at 200 rad and the number occurring at 100 and 400 rad was similar. Kinetics of porcine spermatogonial renewal differs considerably from those of the rodent and, relative to the rodent, this may account for the boar's higher sensitivity to stem-cell killing and lower sensitivity to translocations.     

Multidisciplinary management of childhood sarcoma: time to expand

Current targeted strategies for cancer focus on the blockade of growth factor receptors and the inhibition of angiogenesis. The VEGF pathway has become an attractive target in multiple malignancies, including lung cancer. Bevacizumab, a monoclonal antibody against VEGF, increased survival in non-small-cell lung cancer (NSCLC) patients when added to standard carboplatin/paclitaxel chemotherapy. The pivotal Phase III study (ECOG 4599) in NSCLC showed longer overall survival: 12.3 versus 10.3 months and a higher median progression-free survival of 6.2 versus 4.5 months when chemotherapy was associated with bevacizumab. Benefits were confirmed in terms of progression-free survival in the European Phase III study (AVAiL). Subsequently, bevacizumab gained US FDA and European Medicines Agengy approval as a first-line therapy for advanced NSCLC. Bevacizumab’s safety profile is well established: most adverse events are mild to moderate and can be managed using standard interventions. This article presents an overview of the current data on bevacizumab for NSCLC.