ArticleNature2013
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
153 citing papers in PubMed, 1 synthesis or guideline pooled it, 257 citations in OpenAlex.
- ASSOCIATION OF MTHFR A1298C POLYMORPHISM WITH BREAST CANCER AND/OR OVARIAN CANCER RISK: AN UPDATED META-ANALYSIS.African journal of traditional, complementary, and alternative medicines : AJTCAM · 2016Pooled it
- Trial
- Harnessing genomics for early cancer detection, risk stratification and prevention.Nature genetics · 2026Review
- Gain-of-function PPM1D mutations attenuate ischemic stroke.Cell death and differentiation · 2025Article
- Pediatric Embryonal Rhabdomyosarcoma: An Integrated Study of Clinicopathological Features, Pan-cancer Targeted Next-generation Sequencing, and Chromosomal Microarray Analysis from a Single Institution.Virchows Archiv : an international journal of pathology · 2025Article
- Clonal Hematopoiesis in Cancer and Cardiovascular Disease: JACC: CardioOncology State-of-the-Art Review.JACC. CardioOncology · 2025Review
- Clonal hematopoiesis in myeloid malignancies and solid tumors.Nature cancer · 2025Review
- PPM1D/Wip1 is amplified, overexpressed, and mutated in human non-Hodgkin's lymphomas.Molecular biology reports · 2024Article
- Distinct landscape and clinical implications of therapy-related clonal hematopoiesis.The Journal of clinical investigation · 2024Review
- Exploring evolutionary trajectories in ovarian cancer patients by longitudinal analysis of ctDNA.Clinical chemistry and laboratory medicine · 2024Article
- Article
- Using team-based precision medicine to advance understanding of rare genetic brain disorders.Journal of neurodevelopmental disorders · 2024Review
- Clonal hematopoiesis in the setting of hematopoietic cell transplantation.Seminars in hematology · 2024Article
- Screening Ultra-Large Encoded Compound Libraries Leads to Novel Protein-Ligand Interactions and High Selectivity.Journal of medicinal chemistry · 2024Review
- Article
- PPM1D activity promotes the replication stress caused by cyclin E1 overexpression.Molecular oncology · 2024Article
- Article
- Clonal haematopoiesis - a novel entity that modifies pathological processes in elderly.Cell death discovery · 2023Review
- A Case Study on PPM1D and 9 Other Shared Germline Alterations in a Family.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in Korea.Human genomics · 2023Review
93 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
64 authors at 20 institutions in 2 countries.
Funding
Abstract
Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication. Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case-control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10(-5)), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10(-4)) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10(-9)). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.
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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.