title: Loss of the p53 tumor suppressor activity is associated with negative prognosis of mantle cell lymphoma.
abstract: Mantle cell lymphoma (MCL) is typified by translocation t(11;14)(q13;q32) causing upregulation of cyclin D1 and deregulation of cell cycle. The cyclin D1 activation plays a critical role in MCL pathogenesis but additional oncogenic events, such as aberrations of the ARF/MDM2/p53 pathway are also necessary for progression of the disease. We analyzed the p53 tumor suppressor in tumor tissue of 33 patients with MCL. The p53 status was determined by functional analyses in yeast (FASAY) and by cDNA sequencing. The level of the p53 protein was assessed by immunohistochemistry and immunoblotting. Loss of the p53-specific locus 17p13.3 was detected by FISH. Mutations in the p53 gene were detected in nine samples and they included eight missense mutations and one short deletion causing frame shift and premature stop codon formation in position 169. This mutation was associated with mRNA decay as revealed by sequencing of the p53 gDNA. All eight missense mutations were manifested by accumulation of the p53 protein in nuclei of tumor cells and three of them exhibited loss of the p53-specific locus 17p13.3. The p53 mutations were shown to be a negative prognostic marker in MCL.
authors.affiliation: Department of Pathology, University Hospital Brno, 625 00 Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Stefancikova
authors.forename: Mojmir
authors.initials: M
authors.lastname: Moulis
authors.forename: Pavel
authors.initials: P
authors.lastname: Fabian
authors.forename: Barbora
authors.initials: B
authors.lastname: Ravcukova
authors.forename: Ingrid
authors.initials: I
authors.lastname: Vasova
authors.forename: Jan
authors.initials: J
authors.lastname: Muzik
authors.forename: Jitka
authors.initials: J
authors.lastname: Malcikova
authors.forename: Iva
authors.initials: I
authors.lastname: Falkova
authors.forename: Jana
authors.initials: J
authors.lastname: Slovackova
authors.forename: Jana
authors.initials: J
authors.lastname: Smardova
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D014178:Translocation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1