Alteration and abnormal expression of the c-myc oncogene in human multiple myeloma

Structural alterations of the c-myc oncogene in human Burkitt's lymphoma and mouse plasmacytoma suggest that this oncogene is involved in several B cell neoplasms. The possibility of c-myc alterations in human myeloma has not been explored, probably because the low proliferative activity characteristic of this tumor impairs the propagation of representative cell lines for the performance of adequate cytogenetic studies. This report describes alterations in the c-myc locus with concomitant elevated expression of mRNA in the tumor cells of two of 37 patients with multiple myeloma. In one case, somatic cell hybrid studies revealed that the cloned rearranged DNA was entirely derived from chromosome 8, thus indicating a novel mechanism of c-myc activation different from that in Burkitt's lymphoma. Seven other patients exhibited five- to 12-fold overexpression of c-myc RNA when compared with normal marrow cells. Elevated mRNA expression in about one fourth of our patients suggests that the c-myc oncogene has a pathogenetic role in the evolution of multiple myeloma.