p53 mutation in a case of blastic transformation of follicular lymphoma with double bcl-2 rearrangement (MBR and VCR)

Leuk Lymphoma. 1998 May;29(5-6):595-605. doi: 10.3109/10428199809050919.

Abstract

The bcl-2 gene is rearranged in most cases of follicular lymphoma and the breakpoint clusters are found in two specific regions: mbr and mcr. Rearrangements of the immunoglobulin heavy chain genes (IgH) result in a deregulation of the gene and increased transcription of mRNA for the bcl-2 protein. In cases of rearrangement of the light chains (variant translocations), a third breakpoint has been described at the 5' part of the bcl-2 locus (vcr). In the present case, we report the molecular analysis of an FL transformed into a blastic phase unresponsive to chemotherapy. Molecular studies revealed a typical bcl-2 rearrangement at the major locus (mbr). Vcr rearrangements was also observed with only a single restriction enzyme. At the same time, SSCP analysis of exon 5 of the p53 locus disclosed an abnormal conformer. Direct sequencing revealed a point mutation at codon 163 (A --> G). Immunohistochemical analysis of the affected sites disclosed overexpression of p53 and bcl-2. It is concluded that p53 mutation can contribute to blastic transformation in cases of follicular lymphomas with double rearrangement at the bcl-2 locus (mbr/vcr).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blast Crisis / genetics*
  • Blast Crisis / pathology
  • Codon / genetics
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Exons / genetics
  • Fatal Outcome
  • Female
  • Genes, Immunoglobulin
  • Genes, bcl-2*
  • Genes, p53*
  • Humans
  • Lymphoma, Follicular / genetics*
  • Lymphoma, Follicular / pathology
  • Middle Aged
  • Point Mutation*
  • Polymorphism, Single-Stranded Conformational
  • Translocation, Genetic / genetics*

Substances

  • Codon
  • DNA, Neoplasm