Genotypic and phenotypic characteristics of germline TP53 variant carriers: experience from two cancer genetic counseling units.

Phenotypic/genotypic characterization of 36 germline TP53 carriers identified by clinical testing and multigene panels; stratification by functional classification DNE_LOF vs noDNE_noLOF

In a retrospective series of 36 germline TP53 variant carriers from 18 families (two Spanish oncogenetic units, 2005–2023), 63.9% developed at least one cancer. Carriers identified by multigene panel (MGP) without classic LFS criteria had later onset (median 42 vs 27 years, p=0.011) and none developed LFS 'core' tumors. DNE_LOF functional classification was associated with earlier onset (median 30 vs 47 years for noDNE_noLOF, p=0.034). Eight carriers (34.7%) developed second primary tumors.

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This study characterizes the growing population of TP53 carriers identified outside classic LFS criteria via multigene panels — a group whose management remains debated. DNE_LOF/noDNE_noLOF functional classification could guide surveillance intensity, but these exploratory results require prospective validation in larger cohorts. The high risk of multiple primaries (34.7%) reinforces the importance of intensive multidisciplinary follow-up.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 2/2 · Sample size: 0/1 · Journal quality: 0/1 → Total: 6/10