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

Akif S. Yavuz, Nancy L. Monson, Sule Yavuz, Amrie C. Grammer, Nancy Longo, Hermann J. Girschick, Peter E. Lipsky

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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 2.8kb downstream of the promoter. RGYW (purine, guanine, pyrimidine, A/T) targeting and a significantly lower mutational frequency in naïve 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 naïve 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.

Original languageEnglish (US)
Pages (from-to)485-493
Number of pages9
JournalMolecular Immunology
Volume39
Issue number7-8
DOIs
StatePublished - Nov 2002

    Fingerprint

Keywords

  • B lymphocytes
  • Human
  • Oncogenes
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Cite this