Association of TP53 polymorphisms on the risk of Wilms tumor

Background Molecular factors influencing Wilms tumor (WT) development remain largely unknown. TP53 mutations seem to be restricted to the anaplastic WT subtype. However, TP53 polymorphisms do not have a defined role in the disease. Procedure To assess the impact of TP53 mutations and polymorphisms (...

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Published in:	Pediatric blood & cancer Vol. 61; no. 3; pp. 436 - 441
Main Authors:	Andrade, R.C., Cardoso, L.C.A., Ferman, S.E., Faria, P.S., Seuánez, H.N., Achatz, M.I., Vargas, F.R.
Format:	Journal Article
Language:	English
Published:	United States Blackwell Publishing Ltd 01-03-2014 Wiley Subscription Services, Inc
Subjects:	Child, Preschool Female Genes, p53 Genotype Hematology Humans Infant Kidney Neoplasms - etiology Kidney Neoplasms - genetics Kidney Neoplasms - mortality Male Mutation Oncology Pediatrics PEX4 PIN2 PIN3 Polymorphism, Genetic Risk TP53 Wilms tumor Wilms Tumor - etiology Wilms Tumor - genetics Wilms Tumor - mortality PIN2 PIN3 PEX4 TP53 Wilms tumor
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Summary:	Background Molecular factors influencing Wilms tumor (WT) development remain largely unknown. TP53 mutations seem to be restricted to the anaplastic WT subtype. However, TP53 polymorphisms do not have a defined role in the disease. Procedure To assess the impact of TP53 mutations and polymorphisms (PIN2, PIN3, and PEX4) on risk of development, age at diagnosis, and survival in WT, we analyzed 46 blood DNA samples and 31 fresh tumor DNA samples from 52 patients with WT. Sequencing of TP53 exons 2–11 was performed. Results Tumor DNA analysis revealed TP53 pathogenic missense mutations (p.V197M, p.R213Q, p.R248W, and p.R337C) in four samples (12.9%). Blood DNA samples revealed a novel intronic mutation, IVS2 + 37C > T, in one patient (2.2%). Bilaterality was associated with a twofold decrease in survival (P = 0.00037). Diffuse anaplasia also presented a lower survival probability compared to patients with non‐anaplastic tumors, or with focal anaplasia (P = 0.045). Patients with a TP53 somatic mutation showed survival probability of 37.5% versus 85.0% for patients with no somatic mutations, although the difference was not statistically significant (P = 0.0706). PIN3 duplicated allele was associated with a 20‐month later mean age at diagnosis (P = 0.0084). TP53 PEX4 C allele showed an increased risk for WT development (P = 0.0379). No relationship was found between survival and gender, age at diagnosis, or the less frequent alleles of PIN2, PIN3, and PEX4. Conclusions Our results demonstrate an association between PIN3 and age at diagnosis, as well as an association of PEX4 and risk of development of WT. Pediatr Blood Cancer 2014;61:436–441. © 2013 Wiley Periodicals, Inc.
Bibliography:	ArticleID:PBC24775 ark:/67375/WNG-RMHKTXGD-C Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) - No. 40196/2010-0; No. 476808/2010-3; No. 486599/2012-4; No. 135171/2010-5 istex:9F3BC168611F479514E5983F466159667E72095D ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1545-5009 1545-5017
DOI:	10.1002/pbc.24775