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

摘要

Translocations involving c-my and an lg locus have been reported rarely in human multiple myeloma (MM). Using specific fluores- cence in situ hybridization probes. we show complex karyotypic abnormalities of the c-my or L-my locus in 19 of 20 MM cell lines and approximately 50/100 of advanced primary MM tumors. These abnormalities include unusual and complex translocations and insertions that often juxtapose my with an lgH or lgL locus. For two advanced 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-my occurs as a late event. All informative MM cell lines show mono- allelic expression of c-myc For Burkitt's lymphoma and mouse plasmacytoma tumors. balanced translocation that juxtaposes c- myc with one of the lg loci is an early, invariant event that is mediated by B cell-specific DNA modification mechanisms. By contrast, for MM, dysregulation of c-my apparently is caused principally by complex genomic rearrangements that occur during late stages of MM progression and do not involve B cell-specific DNA modification mechanisms.