Modificadores de penetrância de mutações germinativas no gene TP53 em famílias brasileiras com diagnóstico clínico da síndrome de Li-Fraumeni e Li-Fraumeni like: impacto dos polimorfismos intragênicos do TP53 e de genes / Genetic modifiers of germline TP53 mutation in Brazilian families with Li-Fraumeni and Li-Fraumeni Like syndromes: impact of TP53 intragenic polymorphisms and p53 regulatory genes

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Li-Fraumeni syndrome (LFS) and its variant like (LFL) are associated with germline mutations in the TP53 gene and predispose to a variety of cancers at an earlier age. We analyzed 91 LFS/LFL families from southern Brazil for germline mutations in TP53 and polymorphisms in TP53 (PIN2, PIN3, PEX4) and MDM2 (309T-G). The germline TP53 mutation R337H was found in 44.4% of all families included. In 750 controls from the same region, mutation prevalence was 0.3%. Genotyping of eight unrelated R337H-positive individuals for 29 intragenic TAG SNPs showed that they all shared the same rare haplotype confirming the founder effect for the mutation. Duplication of PIN3 had a modifier effect on the age of tumor onset (delay of 17.1 years) in TP53 mutation carriers whereas MDM2 SNP309 modulated age of onset for soft-tissue sarcomas.

ASSUNTO(S)

carcinoma adrenocortical deleção de genes genetic polymorphism polimorfismo genético síndrome de li-fraumeni genetic predisposition to disease germline mutation proto-oncogene proteins c-mdm2 gene deletion li-fraumeni syndrome tumor suppressor protein p53 adrenocortical carcinoma proteína supressora de tumor p53 mutação em linhagem germinativa proteínas proto-oncogênicas c-mdm2 predisposição genética para doença

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