title: Mechanisms that promote and suppress chromosomal translocations in lymphocytes.
abstract: Recurrent chromosomal translocations are characteristic features of many types of cancers, especially lymphomas and leukemias. Several basic mechanistic factors are required for the generation of most translocations. First, DNA double-strand breaks (DSBs) must be present simultaneously at the two participating loci. Second, the two broken loci must either be in proximity or be moved into proximity to be joined. Finally, cellular DNA repair pathways must be available to join the two broken loci to complete the translocation. These mechanistic factors can vary in different normal and mutant cells and, as a result, substantially influence the frequency at which particular translocations are generated in a given cell type. Ultimately, however, appearance of recurrent oncogenic translocations in tumors is, in most cases, strongly influenced by selection for the translocated oncogene during the tumorigenesis process. In this review, we discuss in depth the factors and pathways that contribute to the generation of translocations in lymphocytes and other cell types. We also discuss recent findings regarding mechanisms that underlie the appearance of recurrent translocations in tumors.
authors.affiliation: Howard Hughes Medical Institute, Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston, Massachusetts 02115, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Gostissa
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
authors.forename: Roberto
authors.initials: R
authors.lastname: Chiarle
mesh_terms: D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007938:Leukemia / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism*; D008223:Lymphoma / Q000235:genetics; D014178:Translocation, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase