Oncogene Activation by Chromosomal Translocations in B Cell-Derived Tumors

摘要: This chapter reviews the current evidence concerning mechanisms of oncogene activation by chromosomal translocations and its role in Burkitt lymphoma (BL), mouse plasmacytoma (MPC), rat immunocytoma (RIC). The following aspects are discussed. (1) Does cis relationship between c-myc one three Ig loci play a causative genesis these tumors? (2) How does juxtaposition activate myc gene? (3) What is functional translocation tumorigenic process? Only first question can be answered with some certainty. In BL, has been found 100% properly investigated cases so far, no difference endemic or nonendemic, EBV-carrying EBV-negative cases. One exceptional line, BJAB, disregarded, since it not typical BL. RIC, all tumors far studied had translocation. MPC, only about 90% MPCs carry translocations. High resolution banding translocation-negative shown that they an interstitial deletion D2/D3 region chromosome 15, corresponding to location gene. Molecular analysis showed complex rearrangement led IgH suites sequences, must have arisen at least two independent inversion. A similarly was RIC examined. regularity association events which occur, together full analogy human, mouse, systems interpreted postulating represents essential step tumors. transposed gene becomes constitutively activated. probability, this renders resistant cell cycle differentiation-dependent regulations govern expression normal location. way contributes escape BL from immune nonimmune controls considered. hypothesis advanced affects B cells point antigen-activated leave proliferative process, upon waning antigenic stimulus, enters program would normally lead toward long-lived memory cell.