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Association of the highly prevalent TP53 R337H mutation with pediatric choroid plexus carcinoma and osteosarcoma in Southeast Brazil
Author(s) -
Seidinger Ana Luiza,
Mastellaro Maria José,
Paschoal Fortes Fernanda,
Godoy Assumpção Juliana,
Aparecida Cardinalli Izilda,
Aparecida Ganazza Mônica,
Correa Ribeiro Raul,
Brandalise Silvia Regina,
dos Santos Aguiar Simone,
Yunes José Andrés
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.25826
Subject(s) - medicine , osteosarcoma , sarcoma , penetrance , choroid plexus , leukemia , cancer research , carcinoma , cancer , rhabdomyosarcoma , oncology , mutation , pathology , genetics , biology , central nervous system , gene , phenotype
BACKGROUND: The inherited, low‐penetrance arginine‐to‐histidine substitution at codon 337 (R337H) of the tumor protein 53 gene ( TP53 ) is clustered in southeast Brazil (estimated frequency, 0.3%). Although its tumorigenic effect initially appeared to be tissue‐specific, recent evidence suggests its association with a broader range of tumors. Therefore, the authors of this report investigated the spectrum of pediatric malignancies associated with the TP53 R337H mutation at a single referral institution in southeast Brazil. METHODS: Genomic DNA samples from 493 children with malignancies were screened for the R337H mutation. Available tumor samples from carriers were investigated for loss of heterozygosity (LOH) and nuclear p53 accumulation. Clinical data were obtained from medical records. RESULTS: Sixty‐five of 70 patients (93%) with adrenocortical tumors (ACTs), 9 of 13 patients (69%) with choroid plexus carcinoma (CPC), and 3 of 41 patients (7.3%) with osteosarcoma carried the mutation. The proportion of CPC to choroid plexus papilloma (CPP) was much higher than that reported elsewhere. Osteosarcoma in carriers had a significantly poorer outcome ( P = .02). The mutation was not identified in patients who had acute lymphoblastic leukemia (ALL) (n = 187), recurrent ALL (n = 49), acute myeloid leukemia (n = 44), lymphoma (n = 30), non‐CPC central nervous system tumors (n = 26), Ewing sarcoma (n = 25), or rhabdomyosarcoma (n = 8). Among the tumors that were available for analysis, LOH with retention of the mutant allele was confirmed in 21 of 21 ACTs, in 2 of 2 CPCs, and in 2 of 3 osteosarcomas that were positive for R337H. CPCs and osteosarcomas that were positive for R337H had marked nuclear accumulation of p53. CONCLUSIONS: The current findings demonstrated compellingly that the TP53 R337H mutation is associated not only with ACT but also with CPC and, to a lesser extent, with osteosarcoma, both of which are core‐component tumors of the Li‐Fraumeni syndrome. Cancer 2011. © 2010 American Cancer Society.