Monosomy 13 is associated with the transition of monoclonal gammopathy of undetermined significance to multiple myeloma

Chromosomal abnormalities are present in most (if not all) patients with mu ltiple myeloma (MM) acid primary plasma cell leukemia (PCL), Furthermore, r ecent data have shown that numerical chromosomal changes are present in mos t individuals with monoclonal gammopathy of undetermined significance (MGUS ). Epidemiological studies have shown that up to one third of MM may emerge from pre-existing MGUS. To clarify further possible stepwise chromosomal a berrations on a pathway between MGUS and MM, we have analyzed 158 patients with either MM or primary PCL and 19 individuals with MGUS using fluorescen ce in situ hybridization (FISH). Our FISH analyses were designed to detect illegitimate IGH rearrangements at 14q32 or monosomy 13, Whereas translocat ions involving the 14q32 region were observed with a similar incidence (60% ) in both conditions, a significant difference was found in the incidence o f monosomy 13 in MGUS versus MM or primary PCL, It was present in 40% of MM /PCL patients, but in only 4 of 19 MGUS individuals, Moreover, whereas mono somy 13 was found in the majority of plasma cells in MM, it was observed on ly in cell subpopulations in MGUS, It is noteworthy that, in a group of 20 patients with MM and a previous MGUS history, incidence of monosomy 13 was 70% versus 31% in MM patients without a known history of MGUS (P = .002), T hus, this study highlights monosomy 13 as correlated with the transformatio n of MGUS to overt MM and may define 2 groups of MM with possible different natural history and outcome, ie, post-MGUS MM with a very high incidence o f monosomy 13 and de novo MM in which other genetic events might be involve d. Serial analyses of individuals with MGUS will be needed to validate this model, (C) 1999 by The American Society of Hematology.