Rare variants in TP53 and susceptibility to neuroblastoma.
J Natl Cancer Inst
; 106(4): dju047, 2014 Apr.
Article
en En
| MEDLINE
| ID: mdl-24634504
ABSTRACT
TP53 is the most frequently mutated gene in human malignancies; however, de novo somatic mutations in childhood embryonal cancers such as neuroblastoma are rare. We report on the analysis of three independent case-control cohorts comprising 10290 individuals and demonstrate that rs78378222 and rs35850753, rare germline variants in linkage disequilibrium that map to the 3' untranslated region (UTR) of TP53 and 5' UTR of the Δ133 isoform of TP53, respectively, are robustly associated with neuroblastoma (rs35850753 odds ratio [OR] = 2.7, 95% confidence interval [CI] = 2.0 to 3.6, P combined = 3.43×10(-12); rs78378222 OR = 2.3, 95% CI = 1.8 to 2.9, P combined = 2.03×10(-11)). All statistical tests were two-sided. These findings add neuroblastoma to the complex repertoire of human cancers influenced by the rs78378222 hypomorphic allele, which impairs proper termination and polyadenylation of TP53 transcripts. Future studies using whole-genome sequencing data are likely to reveal additional rare variants with large effect sizes contributing to neuroblastoma tumorigenesis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Desequilibrio de Ligamiento
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Proteína p53 Supresora de Tumor
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Mutación de Línea Germinal
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Polimorfismo de Nucleótido Simple
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Neuroblastoma
Límite:
Humans
Idioma:
En
Revista:
J Natl Cancer Inst
Año:
2014
Tipo del documento:
Article