Journal Article

DKFZ-2025-00250

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cancer risk in carriers of TP53 germline variants grouped into different functional categories.

Müntnich, L. J. ; Dutzmann, C. M. ; Großhennig, A. ; Härter, V. ; Keymling, M.DKFZ* ; Mastronuzzi, A. ; Montellier, E. ; Nees, J. ; Palmaers, N. E. ; Penkert, J. ; Pfister, S. M.DKFZ* ; Ripperger, T. ; Schott, S. ; Silchmüller, F. ; Hainaut, P. ; Kratz, C. P.

2025
Oxford University Press Oxford

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Please use a persistent id in citations: doi:10.1093/jncics/pkaf008

Abstract: 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.

Keyword(s): TP53 ; Li-Fraumeni syndrome ; genotype-phenotype correlation

Note: 2025 Jan 3;9(1):pkaf008

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Contributing Institute(s):

1. E010 Radiologie (E010)
2. B062 Pädiatrische Neuroonkologie (B062)
3. DKTK HD zentral (HD01)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2025

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Emerging Sources Citation Index ; Fees ; IF < 5 ; JCR ; SCOPUS ; Web of Science Core Collection

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