Point mutations in the c-Myc transactivation domain are common in Burkitt's lymphoma and mouse plasmacytomas.
We have screened the entire coding region of c-myc in a panel of Burkitt's lymphomas (BLs) and mouse plasmacytomas (PCTs). Contrary to the belief that c-myc is wild type in these tumours, we found that 65% of 57 BLs and 30% of 10 PCTs tested exhibit at least one amino acid (aa) substitution. These mutations were apparently homozygous in all BL cell lines tested and two tumour biopsies, implying that the mutations often occur before Myc/Ig translocation in BL. In PCTs, only the mutant c-myc allele was expressed indicating a functional homozygosity, but occurrence of mutations after the translocation. Many of the observed mutations are clustered in regions associated with transcriptional activation and apoptosis, and in BLs, they frequently occur at sites of phosphorylation, suggesting that the mutations have a pathogenetic role.
Bhatia
K
K
Pediatric Branch, Clinical Oncology Program, NCI/NIH, Bethesda, Maryland 20892.
Huppi
K
K
Spangler
G
G
Siwarski
D
D
Iyer
R
R
Magrath
I
I
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005799:Genes, Dominant; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010954:Plasmacytoma / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D016271:Proto-Oncogene Proteins c-myc