title: p53 mutation in a case of blastic transformation of follicular lymphoma with double bcl-2 rearrangement (MBR and VCR).
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).
authors.affiliation: Departament d'Hematologia del Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: J F
authors.initials: JF
authors.lastname: Nomdedéu
authors.forename: M
authors.initials: M
authors.lastname: Baiget
authors.forename: G
authors.initials: G
authors.lastname: Gaidano
authors.forename: C
authors.initials: C
authors.lastname: Estivill
authors.forename: A
authors.initials: A
authors.lastname: Lasa
authors.forename: E
authors.initials: E
authors.lastname: Rubiol
authors.forename: R
authors.initials: R
authors.lastname: Mateu
authors.forename: R
authors.initials: R
authors.lastname: Bordes
authors.forename: S
authors.initials: S
authors.lastname: Brunet
authors.forename: G
authors.initials: G
authors.lastname: Saglio
authors.forename: J
authors.initials: J
authors.lastname: Soler
mesh_terms: D001752:Blast Crisis / Q000235:genetics* / Q000473:pathology; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D005803:Genes, Immunoglobulin; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D003062:Codon; D004273:DNA, Neoplasm