biostudies-literatureCastillo DBreast Cancer Research FoundationNIH Cancer Center Support GrantNCI NIH HHSNIH1621-1629https://www.ebi.ac.uk/biostudies/studies/S-EPMC9866580biostudies-literatureUnknown31(8)<h4>Background</h4>Though germline TP53 pathogenic/likely pathogenic variants (PV) are associated with Li-Fraumeni syndrome, many detected by multigene panels represent aberrant clonal expansion (ACE), most due to clonal hematopoiesis (CH). Discerning ACE/CH from germline variants and postzygotic mosaicism (PZM) is critically needed for risk assessment and management.<h4>Methods</h4>Participants in the Li-Fraumeni &amp; TP53 Understanding &amp; Progress (LiFT UP) study with a TP53 PV were eligible. Demographics, personal/family cancer history, and clinical laboratory test reports were obtained. DNA from multiple tissues was analyzed using a custom QIAseq assay (ACE panel) that included TP53 and other CH-associated genes; the ACE panel and eyebrow follicles were assessed in a workflow to diCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive OncologyClonal Hematopoiesis and Mosaicism Revealed by a Multi-Tissue Analysis of Constitutional TP53 Status.PMC9866580RC4 CA153828P30 CA033572grant nos.20–172R01 CA242218U19 CA203654Mokhnatkin JYang KSlavin TPEbert BLCervantes AWeitzel JNAmos CIHyman SGarber JETsang KKNehoray BHerzog JCastillo DSand SRSchwartz AYuan TAfalseClonal Hematopoiesis and Mosaicism Revealed by a Multi-Tissue Analysis of Constitutional TP53 Status.<h4>Background</h4>Though germline TP53 pathogenic/likely pathogenic variants (PV) are associated with Li-Fraumeni syndrome, many detected by multigene panels represent aberrant clonal expansion (ACE), most due to clonal hematopoiesis (CH). Discerning ACE/CH from germline variants and postzygotic mosaicism (PZM) is critically needed for risk assessment and management.<h4>Methods</h4>Participants in the Li-Fraumeni &amp; TP53 Understanding &amp; Progress (LiFT UP) study with a TP53 PV were eligible. Demographics, personal/family cancer history, and clinical laboratory test reports were obtained. DNA from multiple tissues was analyzed using a custom QIAseq assay (ACE panel) that included TP53 and other CH-associated genes; the ACE panel and eyebrow follicles were assessed in a workflow to di2022-01-01T00:00:00Z2022 Aug2026-05-27T22:41:22.812Z2025-02-19T04:21:04.05ZS-EPMC98665803565436010.1158/1055-9965.epi-21-129610.1158/1055-9965.EPI-21-1296