Different patterns of bcl-6 and p53 gene mutations in tonsillar B cells indicate separate mutational mechanisms.
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.
Yavuz
Akif S
AS
Department of Internal Medicine and Harold C. Simmons Arthritis Research Center, The University of Texas Southwestern Medical Center at Dallas, 20892, USA.
Monson
Nancy L
NL
Yavuz
Sule
S
Grammer
Amrie C
AC
Longo
Nancy
N
Girschick
Hermann J
HJ
Lipsky
Peter E
PE
D001402:B-Lymphocytes / Q000378:metabolism*; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D005803:Genes, Immunoglobulin; D016158:Genes, p53; D006801:Humans; D009154:Mutation / Q000235:genetics*; D014066:Palatine Tonsil / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors