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

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 x 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 nai;ve 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 nai;ve B-cell subsets (1.02 x 10(-3) to 1.25 x 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.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Yavuz AS,Monson NL,Yavuz S,Grammer AC,Longo N,Girschick HJ,Lipsky PE

doi

10.1016/s0161-5890(02)00117-7

subject

Has Abstract

pub_date

2002-11-01 00:00:00

pages

485-93

issue

7-8

eissn

0161-5890

issn

1872-9142

pii

S0161589002001177

journal_volume

39

pub_type

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