Abstract
192 patients with multiple myeloma (MM) and benign monoclonal gammopathy of undetermined significance (MGUS, n=10) were investigated by interphase fluorescence in-situ hybridisation (iFISH) without (n= 132) and with positive plasma cell identification (PC-ID+) (n= 50).
134 were investigated at diagnosis 32 at time of progression, 7 at time of relapse and 9 were investigated with partial remission or no response. 10 of the MM cases were investigated twice. The patients were investigated with FISH probes detecting 11q23 (n=61), 13q13-14 (n=181), 14q32 ((n=121), 17p13.1 (n=181), t(4;14) (n=76) and t(11;14) (n=73). 61/132 (46%) of patients investigated without PC-ID+ showed abnormalities as opposed to 45/49 of evaluable cases (92%) with PC-ID+. The increase in abnormal cases was mainly due to the detection of more cases with loss of 13q and 17p and der(14)(q32): For patients investigated at diagnosis without and with PC-ID+, respectively: 13q-: 17% and 28%, 17p-: 3% and 15%, and 14q split signals (excluding the specific translocations): 8% and 24%. Based on the relatively small number investigated, the t(4;14) and the t(11;14) were not detected more frequently. G-band cytogenetics was carried out in 72 patients (25 without PC-ID+ and 47 with PC-ID+). 19 cases were abnormal (26%). Concordance for 1 or more aberration was found in 14 patients. t(11;14) was detected by both methods in 4 of 5 patients. Out of 7 cases with either near-tetraploidy/triploidy or hypoploidy in the G-band karyotypes, the modal number in the G-banded karyotypes could not be elucidated with certainty in 4 by iFISH with the applied probes. 7/10 patients investigated twice by iFISH showed new abnormalities on reinvestigation, 5 of these had a normal 1st analysis. 3 of 10 MGUS patients showed abnormalities.
In conclusion, PC-ID+ is important for the detection of numerical aberrations and disclosing translocations involving 14q32, as translocations involving the IgH locus are frequent occurring in 64 % (n = 32) at diagnosis. Of these the t(4;14) and the t(11;14) constituted 8% and 20%, respectively. Re-examination of patients with a normal analysis should be considered in non-responders and progressing patients. Lastly, by applying the set of probes we chose in accordance with the proposed recommendations from the European Myeloma Network FISH Workshop, Royal Marsden Hospital, London UK, March 2005, failure to accurately the exsistence of detect near-tetraploid/near-triploid-, and hypoploid clones, is not insignificant (26%) and, based on the small number of cytogenetically abnormal cases it is recommended to include extra probes to classify the patients according to modal number by iFISH.
Jumping Translocations of Chromosome 1q in Multiple Myeloma: Evidence for a Mechanism Involving Decondensation of Pericentromeric Heterochromatin