c-MYC gene abnormalities in high grade and centroblastic-centrocytic non-Hodgkins lymphoma

Fifty nine cases of high grade and centroblastic-centrocytic (cc) Non Hodgkins Lymphoma (NHL) were investigated for mutations and gross gene rearrangements in the 5' region of the c-MYC gene. Mutations in this region, and the presence of hypermutated c-MYC genes, have been associated with poor prognostic groups. All cases showed normal c-MYC gene organisation on Southern blot analysis indicating absence of gross gene rearrangements. PCR amplification and restriction digest analysis of the exon 1/intron 1 region revealed point mutations in 7 cases. No evidence for hypermutation was found. Mutations were relatively more common in high grade NHL (6/39) than in cc-NHL (1/20). There was no correlation with disease status at presentation or relapse or the presence of extranodal disease. The cc-NHL case with a c-MYC mutation subsequently transformed to high grade disease. These data suggest that hypermutation of the c-MYC gene is a relatively rare event in cc-NHL and high grade NHL and does not contribute to the aetiology in the majority of cases. Mutation of c-MYC in cc-NHL may predict transformation to high grade disease.