Gain of 1q21 Does Not Predict for Immediate Progression in MGUS

Abstract 123 In 30% to 40% of multiple myeloma tumours there is a gain of sequences at 1q21. These gains are highly associated with other poor risk cytogenetic features, a high proliferation expression index, poor prognosis and shortened post relapse survival. The abnormality has been reported to be absent or very rare in monoclonal gammopathy of undetermined significance (MGUS), suggesting that it may be a secondary event playing a role in the progression from MGUS to myeloma. Using fluorescence in situ hybridization (FISH) on purified plasma cells, we investigated gain of 1q21 using a BAC probe for CKS1B (1q21.3) in a series of 855 patients (MGUS, 88; myeloma, 767 of which 472 were treated within the context of a national trial) sent from multiple centers throughout the UK. FISH for deletion 13, IgH rearrangements, t(4;14), t(6;14), t(11;14), t(14;16), t(14;20), ploidy status, and deletions of 17p13 and CDKN2C (1p32.3) was also carried out. As expected the incidence of 1q gain was significantly lower in MGUS (20%) than in myeloma (39%) (P=0.001). In the MGUS group, all but 5 cases with the abnormality showed 3 copies of CKS1B; 2 cases showed tetrasomy, while 3 cases showed 5 copies of the gene. Apart from 2 cases where the percentage of plasma cells with the abnormality was low (21% and 26%), the MGUS patients showed the abnormality in the majority of neoplastic cells (median percentage: 87%). In myeloma cases positive for 1q gain the median percentage of affected cells was 94%; in 30% of patients there was gain of a single extra copy; 2 and 3 extra copies were found in 7% and 1% of patients, respectively; 6 cases showed amplification (≥ 6 copies). In myeloma, 1q21 gain was significantly associated with t(4;14), deletion 13, t(14;16), t(14;20) and non-hyperdiploidy (≤ 47 chromosomes) and inversely associated with t(6;14)/t(11;14). In MGUS, given the more limited number of patients, the only significant correlation was the inverted association with t(6;14)/t(11;14). Within the trial myeloma group (median follow-up of 21 mo), patients with 1q21 gain had a significant inferior overall survival compared with those with normal 1q21 copy number (33 mo vs 55 mo, P Disclosures: No relevant conflicts of interest to declare.