The Chromosomal Pattern 14q-Translocation Plus 13q-Deletion Is Characteristic for Multiple Myeloma after a Preceding Monoclonal Gammopathy of Undetermined Significance.

Abstract

Multiple myeloma (MM) may be preceded by a monoclonal gammopathy of undetermined significance (MGUS), but it is at present unclear whether or not MM post-MGUS is biologically and clinically different from MM de-novo. To address this issue, we have performed a molecular cytogenetic analysis of 32 cases of MM post-MGUS (median time between recognition of MGUS and transition to MM, 7.6 years; range, 2.6 years to 19.5 years) and compared the findings with those of 256 patients with MM de-novo, in whom no previous history of MGUS had been documented. FISH studies of clonal plasma cells (cytoplasmic Ig positive) with probes for IgH translocations [t(14q32)], t(11;14)(q13;q32), t(4;14)(p16;q32), and deletion of 13q14 [del(13q14)] revealed results summarized in Table 1: Serial studies of MGUS plasma cells and MM post-MGUS plasma cells from 12 of these patients have thus far indicated that all chromosomal abnormalities observed at MM post-MGUS were already present in the MGUS plasma cells; most notably, there was one patient with t(4;14) plus del(13q) who had both abnormalities at the time of MGUS 94 months prior to transition to MM. Collectively, our data suggest that MM post-MGUS is characterized by a distinct chromosomal pattern, in particular a high frequency of t(14q32) plus del(13q14), frequent occurrence of a t(11;14), but low frequency of a t(4;14). We are currently studying the t(14q32) plus del(13q) chromosomal pattern in MGUS to investigate its potential value as a risk factor for transition from MGUS to MM. Table 1: FISH of MM post-MGUS versus MM de novo Abnormality MM post-MGUS MM de-novo P-value Any t(14q32) 24/32 (75%) 114/256 (44.5%) .05 t(11;14)(q13;q32) 9/32 (28.1%) 32/256 (12.5%) .05 t(4;14)(p16;q32) 2/32 (6.3%) 27/256 (10.6%) .37 del(13q14) 19/32 (59.4%) 102/256 (39.8%) .13 del(13q14) plus t(14q32) 18/19 (94.7%) 57/102 (55.8%) .11 del(13q14) plus t(11;14) 6/19 (31.6%) 9/102 (8.8%) .03

Chromosomal abnormalities of young multiple myeloma patients (<45 yr) are not different from those of other age groups and are independent of stage according to the International Staging System

“…According to our recent findings, the cytogenetic pattern of a 14q‐translocation plus del(13q14) is a characteristic chromosomal finding in MM post‐monoclonal gammopathy of undetermined significance (MGUS)‐(20, 21). However, there were no significant differences between the three MM patient cohorts regarding the frequency of the 14q‐translocation plus del(13q14) pattern (21% in Group A, 32% in Group B, and 15.6% in Group C; P > 0.45).…”

“…Although detailed data are not available on the frequency of MGUS prior to MM, elderly MM patients are more likely to have a disease that evolved from a long‐lasting, pre‐existing MGUS than young MM patients. We have recently observed that the simultaneous occurrence of a 14q‐translocation with a del(13q14) is a characteristic chromosomal pattern in MM patients after a preceding MGUS (21). We therefore included these chromosomal abnormalities as well as chromosomes associated with hyperdiploidy in the present analysis.…”