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.

journal_name

Int J Oncol

authors

Stefancikova L,Moulis M,Fabian P,Ravcukova B,Vasova I,Muzik J,Malcikova J,Falkova I,Slovackova J,Smardova J

doi

10.3892/ijo_00000545

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

699-706

issue

3

eissn

1019-6439

issn

1791-2423

journal_volume

36

pub_type

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