Increased Incidence of Choroid Plexus Carcinoma Due to the Germline TP53 R337H Mutation in Southern Brazil
Open Access
- 22 March 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (3), e18015
- https://doi.org/10.1371/journal.pone.0018015
Abstract
Choroid plexus carcinomas (CPC) are rare tumors predominantly found in children. Given the high frequency of the germline R337H mutation in the TP53 gene in southern Brazil, we have evaluated the frequency of the R337H mutation in families with CPC in children. The present series included 29 patients that were admitted to the same institution from 1992 to 2010, including 22 children with CPC (0.08–13.6 years of age at diagnosis) and 7 children with papilloma of the choroid plexus (Pp; 0.5–9.8 years of age). Surgical resection was possible in 28 children. Blood and/or tumor DNA was extracted and analyzed using PCR-RFLP and results were confirmed by sequencing 240 bp of the TP53 exon 10. The patients, all parents, and some relatives submitted samples for blood DNA analysis. In addition, we have also examined the presence of the mutation in DNA from paraffin-embedded tumor samples to evaluate loss of heterozygosity. We found 63.3% (14/22) of the CPC patients positive for the germline R337H mutation; CPC samples were either heterozygous (n = 7), lost only the wild-type (n = 4), or only the R337H copy (n = 2). One CPC sample was not available. All Pp cases (7/7, 100%) were negative for R337H. Cure (>5 years survival free of disease) was observed in 18.1% of the CPC cases with the R337H mutation (2/11), 71.4% of the Pp (5/7), and 25% of CPC cases negative for the R337H mutation (2/8). Family history of cancer (with 2 or more cancer cases) was exclusively identified on the parental side segregating the R337H mutation, and 50% (7/14) of them were compatible with Li-Fraumeni-like syndrome. Our results show for the first time that the R337H TP53 mutation is responsible for 63% of the CPC cases in children, suggesting a higher incidence of CPC in southern Brazil.Keywords
This publication has 31 references indexed in Scilit:
- Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndromeRadiation Oncology, 2010
- Heterochromatin silencing of p53 target genes by a small viral proteinNature, 2010
- Efficiency evaluation of a DNA extraction and purification protocol on archival formalin-fixed and paraffin-embedded tissueForensic Science International, 2010
- Association of the germline TP53R337H mutation with breast cancer in southern BrazilBMC Cancer, 2008
- The 2007 WHO Classification of Tumours of the Central Nervous SystemActa Neuropathologica, 2007
- Nodule Formation and Desmoplasia in Medulloblastomas—Defining the Nodular/Desmoplastic Variant and Its Biological BehaviorBrain Pathology, 2007
- Tumores de plexo coróide: estudo epidemiológico comparativo de 24 casosArquivos de Neuro-Psiquiatria, 2004
- An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinomaProceedings of the National Academy of Sciences, 2001
- Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumourNature, 1993
- Mutation and Cancer: Statistical Study of RetinoblastomaProceedings of the National Academy of Sciences, 1971