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TP53 c.1000G>C; p.G334R is an Ashkenazi Jewish predominant mutation associated with a low penetrance Li-Fraumeni Syndrome

ABSTRACT: Multiple family members with cancer or individuals with multiple primary cancers are indicative of potential genetic etiology1. Germline mutations in TP53 cause a rare high penetrance cancer syndrome, Li Fraumeni Syndrome (LFS)2. We identified a TP53 tetramerization domain (TD) missense mutation c.1000G>C;p.G334R, in a family with LFS-associated cancers. Twenty-one additional probands were identified, and available tumors showed biallelic somatic inactivation of TP53. The majority of families were of Ashkenazi Jewish descent, and the TP53 c.1000G>C allele was found on a commonly inherited haplotype. While classical p53 target gene activation was maintained in p.G334R mutant cell lines treated with Nutlin-3a, a subset of p53 target genes, including PCLO, PLTP, PLXNB3 and LCN15, showed defective transactivation. Structural analysis demonstrated thermal instability of the mutant TD, and the G334R mutant protein showed increased preponderance of mutant conformation protein. TP53 c.1000G>C;p.G334R is a rare AJ-predominant mutation associated with low penetrance Li-Fraumeni Syndrome

ORGANISM(S): Homo sapiens

PROVIDER: GSE143741 | GEO | 2020/07/24

REPOSITORIES: GEO

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Genomic profiling of TP53 and non-TP53 Li-Fraumeni syndrome tumors reveals hits in the p53 and overlapping pathways

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Genomic profiling of TP53 and non-TP53 Li-Fraumeni syndrome tumors reveals hits in the p53 and overlapping pathways

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TP53 c.1000G>C p.G334R is an Ashkenazi Jewish predominant mutation associated with a low penetrance Li-Fraumeni Syndrome

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