Clinical management of TP53 mosaic variants found on germline genetic testing.

ABSTRACT:

Background

Germline heterozygous TP53 pathogenic variants (PVs) cause Li Fraumeni Syndrome (LFS, OMIM#151623). TP53 PVs at lower-than-expected variant allele frequencies (VAF) may reflect postzygotic mosaicism (PZM) or clonal hematopoiesis (CH); however, no guidelines exist for workup and clinical management.

Patients and methods

Retrospective analysis of probands who presented to an academic cancer genetics program with a TP53 PV result on germline genetic testing.

Results

Twenty-one of 125 unrelated probands (17 %) were found to harbor a TP53 PV with VAF<30 % or a designation of "mosaic". A diagnosis of PZM was made in nine (43 %) due to a clinical phenotype consistent with LFS with (n = 8) or without (n = 1) positive ancillary tissue testing. Twelve patients (57 %)

SUBMITTER: Ward A 

PROVIDER: S-EPMC11168919 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature