Skip to content
DraconiticResearch
Search Sources API
190,860 studies31 sourcesUpdated 20 min ago
Peer-reviewedCC BYBMC cancer

Characterisation of a novel p53 mutation (p53N263Tfs*7) associated with li-fraumeni syndrome.

  • Francesca M Wright1
  • Mariela Vasileva-Slaveva2,3
  • Angel Yordanov4
  • Ivan Ivanov4
  • Zornitsa Gorcheva4
  • Andrea Mohr1
  • Gareth S A Wright1
  • Greg N Brooke5
  • Metodi V Metodiev6,7
7 affiliations
  1. 1School of Life Sciences, University of Essex, Colchester, Essex, CO4 3SQ, UK.
  2. 2Department of Breast Surgery, Shterev Hospital, Sofia, 1000, Bulgaria.
  3. 3Bulgarian Breast and other gynecological Cancers Association, Sofia, 1750, Bulgaria.
  4. 4Medical University of Pleven, Pleven, 5800, Bulgaria.
  5. 5School of Life Sciences, University of Essex, Colchester, Essex, CO4 3SQ, UK. [email protected].
  6. 6School of Life Sciences, University of Essex, Colchester, Essex, CO4 3SQ, UK. [email protected].
  7. 7Medical University of Pleven, Pleven, 5800, Bulgaria. [email protected].
Read full textPDFDOICite

Abstract

Li-Fraumeni Syndrome (LFS) is a hereditary cancer predisposition syndrome caused by germline mutations in the TP53 tumour suppressor gene, which encodes the multifunctional transcription factor p53. p53 is the most commonly mutated protein in human cancer, with the majority occurring within the DNA-binding domain, often disrupting transcriptional activity and resulting in a loss-of-function. Here, we characterise the novel p53N263Tfs*7 truncated mutant, identified as a germline mutation from a patient with LFS who developed breast cancer. Functional assays revealed a partial loss-of-function across key cellular processes, including proliferation, cell death, cell motility, and transcriptional transactivation. This mutant lacked a dominant-negative effect, distinguishing it from common DNA-binding domain missense mutations. Our findings demonstrate that oncogenesis in LFS can be driven by partial impairment of functional p53, rather than dominant-negative or gain-of-function mutations alone. This underscores the clinical significance of recognising subtle TP53 variants for the refined molecular classification and clinical prediction of cancer risk in TP53 mutation carriers.

Related

  1. Li-Fraumeni syndrome presenting with early-onset eyelid sebaceous carcinoma
    Li Lyung Wang, Songji Choi, Hyunji Kim +2
    American Journal of Ophthalmology Case ReportsPeer-reviewedCC BY-NC-NDFull textGeneral medicineDOAJEurope PMCEurope PMCPMC
  2. KCNJ2 gene spontaneous missense mutation in a child with Andersen-Tawil syndrome: a case report
    Meiqi Feng, Xi Wang, Lingshan Hu +1
    Frontiers in PediatricsPeer-reviewedCC BY 4.0Full textCardiovascular medicinePMCEurope PMC
  3. Case Report: Discordant hypertrophic cardiomyopathy in monozygotic twins with LEOPARD syndrome and an identical PTPN11 c.1391G > C (p.Gly464Ala) mutation
    Xin Xue, Yayuan Ning, Fang Yao +2
    Frontiers in Cardiovascular MedicinePeer-reviewedCC BY 4.0Full textCardiovascular medicineCrossrefEurope PMCPMC
  4. The infero-apical left ventricular aneurysm and long QT syndrome caused by mutation delKKP 1504–1506 in SCN5A gene
    Zhijuan Lu, Jiadong Lin, Yi Chen +5
    BMC Medical GenomicsPeer-reviewedCC BYFull textCardiovascular medicineDOAJ
  5. Prenatal diagnosis of CHARGE syndrome in a fetus with a novel CHD7 splicing mutation: A case report.
    Elena Papageorgiou, Christina Keramida, Elissavet Siomou +9
    Experimental and therapeutic medicinePeer-reviewedCC BY-NC-NDFull textHuman geneticsEurope PMCPMC

Cite

BibTeXRIS
BibTeX
@article{wright2026characterisation,
  title = {{Characterisation of a novel p53 mutation (p53N263Tfs*7) associated with li-fraumeni syndrome.}},
  author = {Francesca M Wright and Mariela Vasileva-Slaveva and Angel Yordanov and Ivan Ivanov and Zornitsa Gorcheva and Andrea Mohr and Gareth S A Wright and Greg N Brooke and Metodi V Metodiev},
  journal = {BMC cancer},
  year = {2026},
  month = jul,
  doi = {10.1186/s12885-026-16582-2},
  url = {https://europepmc.org/article/MED/42928139},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Characterisation of a novel p53 mutation (p53N263Tfs*7) associated with li-fraumeni syndrome.
AU  - Francesca M Wright
AU  - Mariela Vasileva-Slaveva
AU  - Angel Yordanov
AU  - Ivan Ivanov
AU  - Zornitsa Gorcheva
AU  - Andrea Mohr
AU  - Gareth S A Wright
AU  - Greg N Brooke
AU  - Metodi V Metodiev
PY  - 2026
DA  - 2026/07/29
JO  - BMC cancer
DO  - 10.1186/s12885-026-16582-2
UR  - https://europepmc.org/article/MED/42928139
AB  - Li-Fraumeni Syndrome (LFS) is a hereditary cancer predisposition syndrome caused by germline mutations in the TP53 tumour suppressor gene, which encodes the multifunctional transcription factor p53. p53 is the most commonly mutated protein in human cancer, with the majority occurring within the DNA-binding domain, often disrupting transcriptional activity and resulting in a loss-of-function. Here, we characterise the novel p53N263Tfs*7 truncated mutant, identified as a germline mutation from a patient with LFS who developed breast cancer. Functional assays revealed a partial loss-of-function across key cellular processes, including proliferation, cell death, cell motility, and transcriptional transactivation. This mutant lacked a dominant-negative effect, distinguishing it from common DNA-binding domain missense mutations. Our findings demonstrate that oncogenesis in LFS can be driven by partial impairment of functional p53, rather than dominant-negative or gain-of-function mutations alone. This underscores the clinical significance of recognising subtle TP53 variants for the refined molecular classification and clinical prediction of cancer risk in TP53 mutation carriers.
SN  - 1471-2407
ER  -