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[Cancer Research 59, 4546-4550, September 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 4546-4550, September 15, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

14q32 Translocations and Monosomy 13 Observed in Monoclonal Gammopathy of Undetermined Significance Delineate a Multistep Process for the Oncogenesis of Multiple Myeloma1

Hervé Avet-Loiseau2, Thierry Facon, Axelle Daviet, Catherine Godon, Marie-José Rapp, Jean-Luc Harousseau, Bernard Grosbois, Régis Bataille and for the Intergroupe Francophone du Myélome

Laboratoire d’Hématologie [H. A-L., A. D., C. G., R. B.] and the Service d’Hématologie Clinique [M-J. R., J-L. H.], Centre Hospitalier Universitaire, 44093 Nantes, France; the Service des Maladies du Sang, Centre Hospitalier Universitaire, 59000 Lille, France [T. F.]; and the Service de Médecine Interne, Centre Hospitalier Universitaire, 35000 Rennes, France [B. G.]

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 performed fluorescence in situ hybridization experiments with probes directed to the 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 present 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 with 12% in MM patients (P = 0.013). Monoallelic deletions of the 13q14 region were found in 21% of patients, with two types of situations. In half of the 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 other half of the evaluable patients (essentially in MGUS patients), it is observed in subclones only. These data enable us to elaborate a plasma cell oncogenesis model from MGUS to MM.




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