Figure 1

Features of some neoplastic chromosomal translocations. Chromosomal translocations in somatic cells are most often encountered in the context of neoplasia. Constitutional translocations arise during gametogenesis or early divisions of the fertilized egg. It is useful to dissect the chromosomal translocation process into two phases: the causes of the breaks and then the rejoining of the four broken ends. [Most chromosomal translocations involve two DSBs, though some can occur during DNA replication (see text).] In neoplastic translocations, the causes of the two DSBs can be different. In this example, one chromosome break is of the CpG-type (see text), and the other can be a V(D)J-type or a random DSB. In addition, breaks can be of the class switch type (CSR-type) or somatic hypermutation type (SHM-type). The V(D)J-type, CSR-type, SHM-type, and CpG-type are limited to lymphoid cells, and further limited by stage of differentiation (see text). Random breaks are thought to be due to oxidative free radicals (reactive oxygen species), ionizing radiation (IR), or topoisomerase failures. The joining of the four DNA ends is done by nonhomologous DNA end joining (NHEJ) in most cases. The causes of the breaks all generate heterogeniety at the break site, and NHEJ creates additional heterogeneity at the joining site. Hence, even when both translocation junctions are sequenced, one can only trace the site or boundary of the original breaks to a zone of at least several nucleotides (often longer, such as 10-20 bp). Less commonly, no nucleotides are lost from either DSB site, and this permits determination of the specific phosphodiester bonds at which the original DSBs occurred. This proved useful for defining the CpG-type break (see text). Some of the specific translocations discussed here have been previously diagrammed in more detail [26–28]. The normal V(D)J and class switch recombination processes have been previously diagrammed [5–9].