Multiple myeloma: Monoallelic deletions of the tumor suppressor genes TP53and RB1 in long-term follow-up

Recently, a working-model of a stepwise malignant transformation in the mol ecular pathogenesis of multiple myeloma (MM) was proposed. involving the tu mor suppressor gene TP53 and retinoblastoma gene (RB1) as prominent compone nts of cell cycle control. To further define the role of TP53 and RB1 in di sease progression, we retrospectively analyzed by fluorescence in situ hybr idization (FISH) cytological material from 16 patients who underwent sequen tial bone marrow biopsies during the course of their disease. For TP53, no deletions were detected at presentation or during follow-up. It is possible that the patients reported here represent a subset with relatively long su rvival, and therefore did nor demonstrate the TP53 deletions that had been reported in patients with a very poor prognosis. For RBI, monoallelic delet ion was demonstrated in nine patients. In each case, the deletion appeared already in the first biopsy analyzed. The presence of a deletion did not af fect the rate of tumor progression or the length of follow-up, and thus pro gnosis. Monoallelic deletions of RBI appear to be a frequent and early even t in the pathogenesis of MM, without obvious relevance for disease progress ion. (C) Elsevier Science Inc., 2000. All rights reserved.