Cancer risk in carriers of TP53 germline variants grouped into different functional categories

Menée à partir de données d'un registre allemand portant sur 304 patients atteints du syndrome de Li-Fraumeni, cette étude analyse le risque de cancer par phénotype en fonction de la classification du variant constitutionnel de TP53

Résumé en anglais

Li-Fraumeni syndrome is a cancer predisposition syndrome caused by pathogenic TP53 germline variants and associated with a high lifelong cancer risk. We analysed the German LFS registry that contains data on 304 individuals. Cancer phenotypes were correlated with variants grouped according to their ability to transactivate target genes in a yeast assay using a traditional (non-functional, partially-functional) and a novel (clusters A, B, C) classification of variants into different groups. Partially-functional and cluster B or C variants were enriched in patients not meeting clinical testing criteria. Time to first malignancy was longer in carriers of partially-functional variants (Hazard Ratio [HR] = 0.38; 95% CI, 0.22 to 0.66). Variants grouped within clusters B (HR = 0.45; 95% CI, 0.28 to 0.71) or C (HR = 0.34; 95% CI, 0.19 to 0.62) were associated with later cancer onset than NULL variants. These findings can be used to risk-stratify patients and inform care.