Detection and possible prognostic relevance of p53 gene mutations in diffuse large B-cell lymphoma. An analysis of 51 cases and review of the literature

Detection and possible prognostic relevance of p53 gene mutations in diffuse large B-cell lymphoma. An analysis of 51 cases and review of the literature

Author Kerbauy, Fábio Rodrigues Autor UNIFESP Google Scholar
Colleoni, Gisele Wally Braga Autor UNIFESP Google Scholar
Saad, Sara Teresinha Olalla Google Scholar
Silva, MRR Google Scholar
Alves, Antonio Correa Autor UNIFESP Google Scholar
Aguiar, Kátia Cilene Carozzi Autor UNIFESP Google Scholar
Albuquerque, Dulcineia M. Autor UNIFESP Google Scholar
Kobarg, J. Google Scholar
Seixas, Maria Teresa Autor UNIFESP Google Scholar
Kerbauy, José Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Estadual de Campinas (UNICAMP)
Ctr Biol Mol Estrutural
Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Although the presence of p53 gene mutations has been considered as a bad prognostic feature in DLBCL, its clinical significance is still controversial. the aims of this study were: detect the presence of mutations in exons 5 to 9 of the p53 gene and correlate it to prognosis in DLBCL. Fifty-one DLBCL patients were enrolled in this study. Expression of p53 was evaluated by immunohistochemistry. the screening of p53 mutations was performed using PCR-SSCP methods. Cases showing a mobility shift on SSCP electrophoresis were analyzed by automatic sequencing. We could identify 8 missense mutations in 6 of 48 cases (12.5%). in addition, we found a known polymorphism at codon 213 and 2 instances of silent mutations. of all mutations/polymorphisms found, 7 (64%) were localized in codons previously described as p53 hot spots in NHL cases. of the remaining alterations (4 or 36%), 2 mutations were localized in codons previously described as hot spots for p53 in other tumors and 2 (codon 142 of the exon 5 and codon 195 of the exon 6), in codons not described as hot spots for p53 up to now. the presence of missense mutations in exons 5 to 9 of p53 gene had adverse impact on overall survival (P=0.020). Cox's Regression Model identified that high-risk International Prognostic Index (IPI) and p53 gene mutations have independent negative impact on OS. Therefore, the association of IPI with cellular factors, such as p53 mutation, can be very helpful in deciding when we should indicate more aggressive therapies in patients with DLBCL, to somehow increase the chance of cure in these patients.
Keywords non-Hodgkin's lymphomas
P53 protein
p53 gene mutation
prognosis
Language English
Date 2004-10-01
Published in Leukemia & Lymphoma. Abingdon: Taylor & Francis Ltd, v. 45, n. 10, p. 2071-2078, 2004.
ISSN 1042-8194 (Sherpa/Romeo, impact factor)
Publisher Taylor & Francis Ltd
Extent 2071-2078
Origin http://dx.doi.org/10.1080/10428190410001713170
Access rights Closed access
Type Article
Web of Science ID WOS:000223523600014
URI http://repositorio.unifesp.br/handle/11600/27974

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