INACTIVATION OF TUMOR-SUPPRESSOR GENES, P53 AND RB1, IN PLASMA-CELL DYSCRASIAS

The role of loss or inactivation of the retinoblastoma (Rb1) and p53 t umor suppressor genes in the pathogenesis of various human malignancie s has been well established, yet little is known regarding plasma cell dyscrasias. In the present study, the loss of Rb1 protein expression, and the presence of Rb1 gene rearrangements as well as the presence o f p53 somatic mutations (exons 5 through 9) were investigated in a pan el of plasma cell dyscrasias, including 15 monoclonal gammopathies of undetermined significance (MGUS), 63 multiple myelomas (MM), and 18 pl asma cell leukemias (PCL). In the same panel of cases, we established the frequency of ras oncogene mutations, the main genetic lesion assoc iated with MM. We report that loss of Rb1 protein and p53 mutations ar e detectable in 34.7 and 9.8% of MM and PCL primary cases; no lesion w as found in MGUS. In advanced stage MM, and PCL cases, Rb1 and p53 ina ctivation, as well as ras mutations were detected. Our findings show t hat Rb1 and p53 inactivation are associated with aggressive plasma cel l dyscrasias, suggesting a role for these lesions in tumor progression rather than initiation.