14q32 translocations and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesisof multiple myeloma

Clonal plasma cells in monoclonal gammopathy of undetermined significance ( MGUS) have been shown to bear copy number chromosome changes. To extend our knowledge of MGUS to structural chromosomal abnormalities, we have perform ed fluorescence in situ hybridization experiments with probes directed to t he 14q32 and 13q14 chromosomal regions in 100 patients with either MGUS or smoldering multiple myeloma (SMM). 14q32 abnormalities were observed in at least 46% of patients with MGUS/SMM , with these abnormalities being presen t in the majority of clonal plasma cells. Whereas t(11;14)(q13;q32) occurs in 15% of MGUS/SMM patients, an incidence similar to that of overt multiple myeloma (MM) patients, translocation t(4;14)(p16;q32) is observed in only 2% of these cases [P = 0.002 for difference with t(11;14)], as compared wit h 12% in MM patients (P = 0.013), Monoallelic deletions of the 13q14 region mere found in 21% of patients, with two types of situations, In half of th e evaluable patients, and especially in patients with SMM, the deletion is present in the majority of clonal plasma cells, as in MM, whereas in the ot her half of the evaluable patients (essentially in MGUS patients), it is ob served in subclones only, These data enable us to elaborate a plasma cell o ncogenesis model from MGUS to MM.