IgH Gene Rearrangements Are Strongly Associated with Hyperdiploidy Variant Multiple Myeloma in Korea: A Contradiction to the Pathogenetic Pathway of IgH Tranlocations in Non Hyperdiploidy Variant.

Recent studies proposed the classification of multiple myeloma (MM) by the pathways involved in the early pathogenesis; nonhyperdiploid variants with a high incidence of IgH translocations and hyperdiploid variants associated with no IgH translocation. Most studies applied cytogenetic study or flow cytometry to define the ploidy. In this study, we combined the cytogenetic results and fluorescent in situ hybridization results to define the ploidy and investigated IgH tranlocation and 13q deletion in relation to the ploidy level on Korean patients with MM. A total of 135 cases diagnosed as MM between 1997 and 2003 from Seoul National University Hospital and the Asan Medical center were enrolled in this study. Conventional cytogenetic studies and FISH studies with different probes specific for the regions containing the genes or chromosomes (RB1, D13S319, D13S25, IgH/FGFR3, IgH/BCL2, IGH dual color, break apart rearrangement probe, IgH/CCND1, 1q, p53, p16, MLL, CEP 7, 11, 12) were performed. Of 135 patients with MM, 62 (45.9%) patients had hyperdiploid karyotype by cytogenetics and FISH. IgH translocations were observed in 37.4% of Korean patients with MM and were more frequent (54.7%) in hyperdiploid variants than in nonhyperdiploid variants (17.4%). Incidence of deletion 13q was 34.7% and also more frequent in hyperdiploid variants (54.2%) than in nonhyperdiploid variants (16.1%). In conclusion, IgH translocations and 13q deletions were not associated with nonhyperdiploid MM and appeared more frequently in hyperdiploid variant in Korean patients with MM.