ArticleBritish journal of cancer2015
Truncating mutations of PPM1D are found in blood DNA samples of lung cancer patients.
Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
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- Article
- Clonal haematopoiesis and cardiovascular disease, defining risk, filling gaps, and framing the future.NPJ cardiovascular health · 2026Review
- Clonal Hematopoiesis of Indeterminate Potential Influences Breast Cancer Outcomes in a Genotype-Specific Manner.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Ageing, immune fitness and cancer.Nature reviews. Cancer · 2025Review
- Clonal Hematopoiesis in Cancer and Cardiovascular Disease: JACC: CardioOncology State-of-the-Art Review.JACC. CardioOncology · 2025Review
- Hematopoietic-specific heterozygous loss of Dnmt3a exacerbates colitis-associated colon cancer.The Journal of experimental medicine · 2023Article
- Article
- A Case Study on PPM1D and 9 Other Shared Germline Alterations in a Family.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- CHIP Happens: Clonal Hematopoiesis of Indeterminate Potential and Its Relationship to Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
- Molecular and clinical aspects relevant for counseling individuals with clonal hematopoiesis of indeterminate potential.Frontiers in oncology · 2023Review
- [Importance of clonal hematopoiesis for hematologic neoplasms].Innere Medizin (Heidelberg, Germany) · 2022Review
- Clonal hematopoiesis: Mutation-specific adaptation to environmental change.Cell stem cell · 2022Review
- Somatic Mutations of Hematopoietic Cells Are an Additional Mechanism of Body Aging, Conducive to Comorbidity and Increasing Chronification of Inflammation.Biomedicines · 2022Review
- Clonal Hematopoiesis: Role in Hematologic and Non-Hematologic Malignancies.Mediterranean journal of hematology and infectious diseases · 2022Review
- Inhibition of the DNA damage response phosphatase PPM1D reprograms neutrophils to enhance anti-tumor immune responses.Nature communications · 2021Article
- Pharmacological Inhibition of WIP1 Sensitizes Acute Myeloid Leukemia Cells to the MDM2 Inhibitor Nutlin-3a.Biomedicines · 2021Article
- The transcriptional landscape of Shh medulloblastoma.Nature communications · 2021Article
- Cardiovascular Disease, Aging, and Clonal Hematopoiesis.Annual review of pathology · 2020Review
- Detectible mosaic truncating PPM1D mutations, age and breast cancer risk.Journal of human genetics · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPPM1D (WIP1) negatively regulates by dephosphorylation many proteins including p53 tumour suppressor. The truncating mutations (nonsense and frameshift) in exon 6 of PPM1D were found recently in blood cells of patients with breast, ovarian or colorectal cancer. These mutants code for gain-of-function PPM1D with retained phosphatase activity. Their significance in carcinogenesis is unknown.
methodsThe exon 6 of PPM1D was sequenced in blood DNA of 543 non-small-cell lung cancer patients (NSCLC). The functional significance of selected PPM1D alterations (Arg458X, Lys469Glu) was compared with the wild-type gene and examined by recombinant DNA techniques, immunoblotting and luciferase reporter assays.
resultsThe frameshift mutations were found in five NSCLC patients (5/543; 0.92%), all of them had squamous cell carcinomas (5/328; 1.5%). All patients with the mutations were exposed, before the blood collection, to the DNA damaging agents as a part of chemotherapeutic regimen. Functional tests demonstrated that truncating mutation Arg458X causes enhancement of dephosphorylation activity of PPM1D toward serine 15 of p53, whereas Lys469Glu version is equivalent to the wild-type. Neither version of PPM1D (wild-type, Arg458X, Lys469Glu) significantly modulated the ability of p53 to transactivate promoters of the examined p53-target genes (BAX and MDM2).
conclusionsThe truncating mutations of PPM1D are present in blood DNA of NSCLC patients at frequency similar to percentage determined for ovarian cancer patients. Our findings raise a question if the detected lesions are a result of chemotherapy.
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