RAS gene mutations in multiple myeloma and related monoclonal gammopathies

The presence of RAS gene mutations in precancerous lesions suggests that they participate in the early stages of neoplastic development. Furthermore, neoplastic progression from monoclonal gammopathy of undetermined significance (MGUS) to overt multiple myeloma (MM) have been frequently observed. These observations prompted us to study the pathogenetic role of RAS genes in MM and related monoclonal gammopathies. DNA from 18 patients with monoclonal gamma-globulinemia including 12 MM were investigated for the presence of N- and K-RAS gene mutations by polymerase chain reaction (PCR)/oligonucleotide hybridization. Mutations involving codons 12, 13 or 61 of N-RAS gene were identified in 3 of the 12 MM patients, 1 of the solitary plasmacytoma patients and none of the 3 of the MGUS patients. In the case of plasmacytoma, RAS mutations were detected in his bone marrow specimens.