ArticleHuman molecular genetics2017
Germline TP53 mutations result into a constitutive defect of p53 DNA binding and transcriptional response to DNA damage.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Genotypic and phenotypic characteristics of germline TP53 variant carriers: experience from two cancer genetic counseling units.Familial cancer · 2026Article
- A Computational Approach for the Prediction of p53 and BCL-2 Protein-Protein Interactions.International journal of molecular sciences · 2025Article
- Deciphering dual clinical entities associated with TP53 pathogenic variants: Insights from 53,085 HBOC panel analyses in French laboratories.International journal of cancer · 2025Article
- TP53 germline testing and hereditary cancer: how somatic events and clinical criteria affect variant detection rate.Genome medicine · 2025Article
- Germline sequence variation in cancer genes in Rwandan breast and prostate cancer cases.NPJ genomic medicine · 2024Article
- Association ofmedRxiv : the preprint server for health sciences · 2023Article
- The Advantages of Next-Generation Sequencing Molecular Classification in Endometrial Cancer Diagnosis.Journal of clinical medicine · 2023Article
- Peripheral precocious puberty in Li-Fraumeni syndrome: a case report and literature review of pure androgen-secreting adrenocortical tumors.Journal of medical case reports · 2023Review
- Common activities and predictive gene signature identified for genetic hypomorphs ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Blood functional assay for rapid clinical interpretation of germlineJournal of medical genetics · 2021Article
- A first report of a rare TP53 variant associated with Li-Fraumeni syndrome manifesting as invasive breast cancer and malignant solitary fibrous tumor.World journal of surgical oncology · 2021Article
- The Enigmatic Role of TP53 in Germ Cell Tumours: Are We Missing Something?International journal of molecular sciences · 2021Review
- Prevalence and Clinicopathological Characteristics of Moderate and High-Penetrance Genes in Non-BRCA1/2 Breast Cancer High-Risk Spanish Families.Journal of personalized medicine · 2021Article
- Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants.Human mutation · 2021Article
- Clinical and molecular characterization of patients fulfilling Chompret criteria for Li-Fraumeni syndrome in Southern Brazil.PloS one · 2021Article
- New surveillance guidelines for Li-Fraumeni and hereditary TP53 related cancer syndrome: implications for germline TP53 testing in breast cancer.Familial cancer · 2021Article
- Prevalence of the BrazilianFrontiers in genetics · 2021Article
- GermlineCancers · 2020Review
- Guidelines for the Li-Fraumeni and heritable TP53-related cancer syndromes.European journal of human genetics : EJHG · 2020Article
- Transcriptional mutagenesis dramatically alters genome-wide p53 transactivation landscape.Scientific reports · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Li-Fraumeni Syndrome (LFS) results from heterozygous germline mutations of TP53, encoding a key transcriptional factor activated in response to DNA damage. We have recently shown, from a large LFS series, that dominant-negative missense mutations are the most clinically severe and, thanks to a new p53 functional assay in lymphocytes, that they alter the p53 transcriptional response to DNA damage more drastically than null mutations. In this study, we first confirmed this observation by performing the p53 functional assay in lymphocytes from 56 TP53 mutation carriers harbouring 35 distinct alterations. Then, to compare the impact of the different types of germline TP53 mutations on DNA binding, we performed chromatin immunoprecipitation-sequencing (ChIP-Seq) in lymphocytes exposed to doxorubicin. ChIP-Seq performed in wild-type TP53 control lymphocytes accurately mapped 1287 p53-binding sites. New p53-binding sites were validated using a functional assay in yeast. ChIP-Seq analysis of LFS lymphocytes carrying TP53 null mutations (p.P152Rfs*18 or complete deletion) or the low penetrant 'Brazilian' p.R337H mutation revealed a moderate decrease of p53-binding sites (949, 580 and 620, respectively) and of ChIP-Seq peak depths. In contrast, analysis of LFS lymphocytes with TP53 dominant-negative missense mutations p.R273H or p.R248W revealed only 310 and 143 p53-binding sites, respectively, and the depths of the corresponding peaks were drastically reduced. Altogether, our results show that TP53 mutation carriers exhibit a constitutive defect of the transcriptional response to DNA damage and that the clinical severity of TP53 dominant-negative missense mutations is explained by a massive and global alteration of p53 DNA binding.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.