LMO T-cell translocation oncogenes typify genes activated by chromosomal translocations that alter transcription and developmental processes
- Medical Research Council (MRC) Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge CB2 2QH, UK
This extract was created in the absence of an abstract.
The cytogenetic analysis of tumors, particularly those of hematopoietic origin, has revealed that reciprocal chromosomal translocations are recurring features of these tumors. Further from the initial recognition of the translocation t(9;22) (Nowell and Hungerford 1960; Rowley 1973), it has become clear that particular chromosomal translocations are found consistently in specific tumor subtypes. A principle example of this is the translocation t(8;14)(q24;q32.1) invariably found in the human B cell tumor Burkitt’s lymphoma (Manolov and Manolov 1972; Zech et al. 1976). The link with the immunoglobulin H-chain locus on chromosome 14, band q32.1 (Croce et al. 1979; Hobart et al. 1981) and subsequently with the K light-chain locus on chromosome 2, band p12 (Malcolm et al. 1982), suggested that the immunoglobulin genes might be associated with the translocation breakpoints. The cloning of the CMYC proto-oncogene associated with the IgH locus from Burkitt’s lymphoma translocation breakpoint t(8;14)(q24;q32) confirmed this. Through the subsequent cloning of the chromosomal breakpoints in other tumors and identification of oncogenes at many different breakpoints, followed by transgenic (Adams and Cory 1991) and homologous recombination knockin analysis (Corral et al. 1996), it has become clear that abnormal tumor-associated chromosomal translocations are important in the etiology of tumors (for review, see Rabbitts 1994). The scientific challenge of the last decade has been to define the contribution of the genes activated by translocations to the course of tumor development and to ascertain whether any general principles can be determined about these ‘translocation’ genes.
There are two main outcomes of chromosomal translocations in human tumors (for review, see Rabbitts 1994). The first is confined to the lymphoid tumors in which the process of antigen receptor gene rearrangement (immunoglobulin or T-cell receptor) occurs and occasionally mediates chromosomal translocation. This type of translocation causes oncogene activation resulting from the new chromosomal environment …
