ArticleProceedings of the National Academy of Sciences of the United States of America2014
Whole-genome sequencing analysis of phenotypic heterogeneity and anticipation in Li-Fraumeni cancer predisposition syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02289326 (Biomarker Monitoring for a Young Individual Carrying a TP53 Gene Mutation in a Familial High-Cancer Predisposition Setting), which is not on this map. Cited by 17 papers.
What it found
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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.
Biomarker Monitoring for a Young Individual Carrying a TP53 Gene Mutation in a Familial High-Cancer Predisposition Setting
Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Multiple Germline Events Contribute to Cancer Development in Patients with Li-Fraumeni Syndrome.Cancer research communications · 2023Article
- Genetic modifiers of p53: opportunities for breast cancer therapies.Oncotarget · 2023Article
- Genetic and stochastic influences upon tumor formation and tumor types in Li-Fraumeni mouse models.Life science alliance · 2021Article
- Article
- Synchronous choroid plexus papilloma and Wilms tumor in a girl, disclosing a Li-Fraumeni syndrome.Hereditary cancer in clinical practice · 2021Article
- Genetic predisposition to neural crest-derived tumors: revisiting the role of KIF1B.Endocrine connections · 2020Article
- Li-Fraumeni syndrome heterogeneity.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- Family-based germline sequencing in children with cancer.Oncogene · 2019Review
- Hematologic malignancies and Li-Fraumeni syndrome.Cold Spring Harbor molecular case studies · 2019Review
- Exome-wide analysis of bi-allelic alterations identifies a Lynch phenotype in The Cancer Genome Atlas.Genome medicine · 2018Article
- Rlip depletion prevents spontaneous neoplasia in TP53 null mice.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- RareNPJ genomic medicine · 2018Article
- Clinical characteristics and registry-validated extended pedigrees of germline TP53 mutation carriers in Denmark.PloS one · 2018Article
- All in the family? Analyzing the impact of family history in addition to genotype on medullary thyroid carcinoma aggressiveness in MEN2A patients.Familial cancer · 2017Article
- The Role of the p53 Protein in Stem-Cell Biology and Epigenetic Regulation.Cold Spring Harbor perspectives in medicine · 2016Review
- Genetic and functional analysis of a Li Fraumeni syndrome family in China.Scientific reports · 2016Article
- Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
Abstract
The Li-Fraumeni syndrome (LFS) and its variant form (LFL) is a familial predisposition to multiple forms of childhood, adolescent, and adult cancers associated with germ-line mutation in the TP53 tumor suppressor gene. Individual disparities in tumor patterns are compounded by acceleration of cancer onset with successive generations. It has been suggested that this apparent anticipation pattern may result from germ-line genomic instability in TP53 mutation carriers, causing increased DNA copy-number variations (CNVs) with successive generations. To address the genetic basis of phenotypic disparities of LFS/LFL, we performed whole-genome sequencing (WGS) of 13 subjects from two generations of an LFS kindred. Neither de novo CNV nor significant difference in total CNV was detected in relation with successive generations or with age at cancer onset. These observations were consistent with an experimental mouse model system showing that trp53 deficiency in the germ line of father or mother did not increase CNV occurrence in the offspring. On the other hand, individual records on 1,771 TP53 mutation carriers from 294 pedigrees were compiled to assess genetic anticipation patterns (International Agency for Research on Cancer TP53 database). No strictly defined anticipation pattern was observed. Rather, in multigeneration families, cancer onset was delayed in older compared with recent generations. These observations support an alternative model for apparent anticipation in which rare variants from noncarrier parents may attenuate constitutive resistance to tumorigenesis in the offspring of TP53 mutation carriers with late cancer onset.
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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.