Dysregulation of c-myc in multiple myeloma.
Translocation of c-myc to IgH switch regions, or less frequently to one of the IgL loci, is essentially an invariant event in murine plasmacytomas. This results in dysregulation of c-myc, manifested by selective expression of the translocated allele. Human multiple myeloma (MM) has a similarly high incidence of translocations involving IgH switch regions, but c-myc is infrequently involved as a partner in these translocations. However, in screening a panel of 20 MM cell lines, we identified six lines containing two genetically distinguishable c-myc alleles. For these six informative lines (and the corresponding tumor for one line) there is selective expression of one c-myc allele despite the apparent absence of translocation, DNA rearrangement, or amplification involving c-myc. This result suggests frequent tumor specific cis-dysregulation of c-myc in MM by a presently unknown mechanism.
Kuehl
W M
WM
NCI-Navy Medical Oncology Branch, Bethesda, MD 20889, USA.
Brents
L A
LA
Chesi
M
M
Huppi
K
K
Bergsagel
P L
PL
D000483:Alleles; D000818:Animals; D004273:DNA, Neoplasm / Q000235:genetics; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D051379:Mice; D009101:Multiple Myeloma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains