Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma

Translocations involving c-myc and an Ig locus have been reported rarely in human multiple myeloma (MM). Using specific fluorescence in situ hybridiza tion probes, we show complex karyotypic abnormalities of the c-myc or L-myc locus in 19 of 20 MM cell lines and approximately 50% of advanced primary MM tumors. These abnormalities include unusual and complex translocations a nd insertions that often juxtapose myc with an IgH or IgL locus. For two ad vanced primary MM tumors, some tumor cells contain a karyotypic abnormality of the c-myc locus, whereas other tumor cells do not, indicating that this karyotypic abnormality of c-myc occurs as a late event. All informative MM cell lines show monoallelic expression of c-myc. For Burkitt's lymphoma an d mouse plasmacytoma tumors, balanced translocation that juxtaposes c-myc w ith one of the Ig loci is an early, invariant event that is mediated by B c ell-specific DNA modification mechanisms. By contrast, for MM, dysregulatio n of c-myc apparently is caused principally by complex genomic rearrangemen ts that occur during late stages of MM progression and do not involve B cel l-specific DNA modification mechanisms.