title: c-MYC gene abnormalities in high grade and centroblastic-centrocytic non-Hodgkins lymphoma.
abstract: 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.
authors.affiliation: Leukaemia Research Fund Laboratory, Medical School, Newcastle upon Tyne, UK.
authors.forename: M
authors.initials: M
authors.lastname: Levasseur
authors.forename: P G
authors.initials: PG
authors.lastname: Middleton
authors.forename: B
authors.initials: B
authors.lastname: Angus
authors.forename: S J
authors.initials: SJ
authors.lastname: Proctor
authors.forename: J
authors.initials: J
authors.lastname: Norden
authors.forename: M R
authors.initials: MR
authors.lastname: Howard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D005260:Female; D015321:Gene Rearrangement; D016259:Genes, myc; D006801:Humans; D007438:Introns; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm