Genome-First Approach of the Prevalence and Cancer Phenotypes of Pathogenic or Likely Pathogenic Germline TP53 Variants.

ABSTRACT: Pathogenic or likely pathogenic (P/LP) germline TP53 variants are the primary cause of Li-Fraumeni syndrome (LFS), a hereditary cancer predisposition disorder characterized by early-onset cancers. The population prevalence of P/LP germline TP53 variants is estimated to be approximately one in every 3,500-20,000 individuals. However, these estimates are likely impacted by ascertainment biases and lack of clinical and genetic data to account for potential confounding factors, such as clonal hematopoiesis. Genome-first approaches of cohorts linked to phenotype data can further refine these estimates by identifying individuals with variants of interest and then assessing their phenotypes. This study evaluated P/LP germline (variant allele fraction ≥ 30%) TP53 variants in three cohorts: UK Biob

SUBMITTER: de Andrade KC 

PROVIDER: S-EPMC10589747 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature