Different patterns of bcl-6 and p53 gene mutations in tonsillar B cells indicate separate mutational mechanisms

• Published in: Molecular immunology Vol. 39; no. 7; pp. 485 - 493
• Main Authors: Yavuz, Akif S, Monson, Nancy L, Yavuz, Sule, Grammer, Amrie C, Longo, Nancy, Girschick, Hermann J, Lipsky, Peter E
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-11-2002
• Subjects: B lymphocytes; B-Lymphocytes - metabolism; Child; DNA-Binding Proteins - genetics; Genes, Immunoglobulin; Genes, p53; Human; Humans; Mutation - genetics; Oncogenes; Palatine Tonsil - immunology; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-6; T lymphocytes; Transcription Factors - genetics; Human; T lymphocytes; B lymphocytes; Oncogenes
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/S0161-5890(02)00117-7

Mutations within the 5′-non-coding region of the bcl-6 gene can occur in lymphomas that originate from germinal centers (GCs), as well as in normal memory and GC B cells. Mutations in the p53 gene occur in 50% of human cancers. Since both bcl-6 and p53 can be mutated in certain circumstances, we investigated the accumulation of mutations in these genes in individual tonsillar B and T cells to determine whether the mutations exhibited a pattern anticipated from the B-cell hypermutation machinery. In tonsillar GC B cells, the overall mutational frequencies in the 5′-non-coding region of the bcl-6 gene was 0.85×10
−3/bp. In contrast, there were no mutations in a region 2.8
kb downstream of the promoter. RGYW (purine, guanine, pyrimidine, A/T) targeting and a significantly lower mutational frequency in naı̈ve B and GC founder B cells compared with GC B cells suggested that a similar mutator mechanism was active on Ig genes and this non-Ig gene. The mutational frequency in the exon-7-region of p53 was similar in the GC, memory and naı̈ve B-cell subsets (1.02×10
−3 to 1.25×10
−3/bp). RGYW/WRCY motifs were not targeted preferentially in the p53 gene. Moreover, a comparable mutational frequency of p53 was noted in tonsillar B and T cells. Hence, mutations in p53 do not appear to be the result of the B-cell hypermutational mechanism.