Open AccessLoss of the p53 tumor suppressor activity is associated with negative prognosis of mantle cell lymphoma
Author(s) -
Lenka Štefančíková,
Mojmír Moulis,
Pavel Fabián,
Barbora Ravčuková,
Ingrid Vášová,
Jan Mužı́k,
Jitka Malčíková,
Iva Falková,
Jana Slováčková,
Jana Šmardová
Publication year - 2010
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo_00000545
Subject(s) - biology , cyclin d1 , mantle cell lymphoma , cancer research , missense mutation , tumor suppressor gene , oncogene , cell cycle , microbiology and biotechnology , mdm2 , lymphoma , gene , genetics , mutation , carcinogenesis , immunology
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.