POINT MUTATIONS IN THE C-MYC TRANSACTIVATION DOMAIN ARE COMMON IN BURKITTS-LYMPHOMA AND MOUSE PLASMACYTOMAS

We have screened the entire coding region of c-myc in a panel of Burki tt's lymphomas (BLs) and mouse plasmacytomas (PCTs). Contrary to the b elief that c-myc is wild type in these tumours, we found that 65% of 5 7 BLs and 30% of 10 PCTs tested exhibit at least one amino acid (aa) s ubstitution. These mutations were apparently homozygous in all BL cell lines tested and two tumour biopsies, implying that the mutations oft en occur before Myc/Ig translocation in BL. In PCTs, only the mutant c -myc allele was expressed indicating a functional homozygosity, but oc currence of mutations after the translocation. Many of the observed mu tations are clustered in regions associated with transcriptional activ ation and apoptosis, and in BLs, they frequently occur at sites of pho sphorylation, suggesting that the mutations have a pathogenetic role.