Molecular mechanisms of chromosome translocation in human B- and T-cell neoplasia.
Our understanding of the molecular biology of many tumors is still rudimentary. The genes involved in most solid tumors, and the mechanisms giving rise to their activation, are virtually unknown. In contrast, for hematopoietic malignancies, we have identified several genes important in oncogenesis, and we understand in at least a limited sense the mechanisms by which translocations impart these genes with the capacity to support malignant growth. It is becoming increasingly apparent that these mechanisms involve very subtle changes in the pattern of gene expression. Similarly, the studies on the mechanisms of chromosome translocation described here underscore the proposition that malignancy may arise by slight perturbations of normal function. The enzymes that physiologically recombine Ig and TCR genes do so with high fidelity under normal circumstances. But occasionally misrecognition of target sequences may lead to chromosome translocation and neoplasia. A deeper understanding of this process will be facilitated by a more certain grasp of normal B- and T-lymphocyte differentiation and proliferation.
Haluska
F G
FG
Wistar Institute, Philadelphia, Pennsylvania 19104.
Croce
C M
CM
D001402:B-Lymphocytes; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics; D002454:Cell Differentiation; D002877:Chromosomes, Human / Q000648:ultrastructure; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D007945:Leukemia, Lymphoid / Q000235:genetics; D008223:Lymphoma / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000235:genetics; D008969:Molecular Sequence Data; D013601:T-Lymphocytes; D014178:Translocation, Genetic