ArticleProceedings of the National Academy of Sciences of the United States of America2002
Missense mutations but not allelic variants alter the function of ATM by dominant interference in patients with breast cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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
49 citing papers in PubMed, 224 citations in OpenAlex.
- Ataxia telangiectasia mutated (ATM) kinase as a predictive biomarker in clinical oncology: implications for a precision treatment approach.Neoplasia (New York, N.Y.) · 2026Review
- Reclassification of ATM Missense Variants of Uncertain Significance by Integrating Results from Systematic Functional Assays into an ACMG Points-Based Framework.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline ATM sequence variants.American journal of human genetics · 2024Article
- Specifications of the ACMG/AMP variant curation guidelines for the analysis of germlinemedRxiv : the preprint server for health sciences · 2024Article
- Value of the loss of heterozygosity to BRCA1 variant classification.NPJ breast cancer · 2022Article
- Review
- A combination of PARP and CHK1 inhibitors efficiently antagonizes MYCN-driven tumors.Oncogene · 2021Article
- NGS in Hereditary Ataxia: When Rare Becomes Frequent.International journal of molecular sciences · 2021Article
- Review
- Rare deleterious germline variants and risk of lung cancer.NPJ precision oncology · 2021Article
- Breast Cancer Adjuvant Radiotherapy in BRCA1/2, TP53, ATM Genes Mutations: Are There Solved Issues?Breast cancer (Dove Medical Press) · 2021Review
- Review
- NF1 patient missense variants predict a role for ATM in modifying neurofibroma initiation.Acta neuropathologica · 2020Article
- ATM, ATR and DNA-PKcs kinases-the lessons from the mouse models: inhibition ≠ deletion.Cell & bioscience · 2020Review
- Inherited Variants inCancers · 2019Article
- A single synonymous mutation determines the phosphorylation and stability of the nascent protein.Journal of molecular cell biology · 2019Article
- Genetic variants in ATM, H2AFX and MRE11 genes and susceptibility to breast cancer in the polish population.BMC cancer · 2018Article
- Homology-Directed Repair and the Role of BRCA1, BRCA2, and Related Proteins in Genome Integrity and Cancer.Annual review of cancer biology · 2018Article
- Rare germline variants in known melanoma susceptibility genes in familial melanoma.Human molecular genetics · 2017Article
- MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated.Nature communications · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human genetic disorder ataxia-telangiectasia (A-T) is characterized by hypersensitivity to ionizing radiation and an elevated risk of malignancy. Epidemiological data support an increased risk for breast and other cancers in A-T heterozygotes. However, screening breast cancer cases for truncating mutations in the ATM (A-T mutated) gene has failed largely to reveal an increased incidence in these patients. It has been hypothesized that ATM missense mutations are implicated in breast cancer, and there is some evidence to support this. The presence of a large variety of rare missense variants in addition to common polymorphisms in ATM makes it difficult to establish such a relationship by association studies. To investigate the functional significance of these changes we have introduced missense substitutions, identified in either A-T or breast cancer patients, into ATM cDNA before establishing stable cell lines to determine their effect on ATM function. Pathogenic missense mutations and neutral missense variants were distinguished initially by their capacity to correct the radiosensitive phenotype in A-T cells. Furthermore missense mutations abolished the radiation-induced kinase activity of ATM in normal control cells, caused chromosome instability, and reduced cell viability in irradiated control cells, whereas neutral variants failed to do so. Mutant ATM was expressed at the same level as endogenous protein, and interference with normal ATM function seemed to be by multimerization. This approach represents a means of identifying genuine ATM mutations and addressing the significance of missense changes in the ATM gene in a variety of cancers including breast cancer.
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.