ArticleOncogene2008
The DNA damage signalling kinase ATM is aberrantly reduced or lost in BRCA1/BRCA2-deficient and ER/PR/ERBB2-triple-negative breast cancer.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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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.
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Who cites it
60 citing papers in PubMed, 113 citations in OpenAlex.
- Trial
- Prognostic Significance of DNA Repair Gene mRNA Expression in Early-Stage Breast Cancer: Insights into Clinical Relevance.Oncology research · 2026Article
- Integrative Machine Learning Model for Overall Survival Prediction in Breast Cancer Using Clinical and Transcriptomic Data.Biology · 2025Article
- DNA damage response in breast cancer and its significant role in guiding novel precise therapies.Biomarker research · 2024Review
- APIR: Aggregating Universal Proteomics Database Search Algorithms for Peptide Identification with FDR Control.Genomics, proteomics & bioinformatics · 2024Article
- Triple-Negative Breast Cancer and Emerging Therapeutic Strategies: ATR and CHK1/2 as Promising Targets.Cancers · 2024Review
- miR-135a-5p overexpression in peripheral blood-derived exosomes mediates vascular injury in type 2 diabetes patients.Frontiers in endocrinology · 2023Article
- Genetic Heterogeneity, Tumor Microenvironment and Immunotherapy in Triple-Negative Breast Cancer.International journal of molecular sciences · 2022Review
- Article
- Review
- ATM kinase regulates tumor immunoreactions in lymphocyte-predominant breast cancer through modulation of NKG2D ligand and TNF cytokines on tumor cells.Medical molecular morphology · 2020Article
- Association of Tumor Protein p53 and Ataxia-Telangiectasia Mutated Comutation With Response to Immune Checkpoint Inhibitors and Mortality in Patients With Non-Small Cell Lung Cancer.JAMA network open · 2019Article
- RECQL5 plays an essential role in maintaining genome stability and viability of triple-negative breast cancer cells.Cancer medicine · 2019Article
- Expression of DNA Damage Response Proteins and Associations with Clinicopathologic Characteristics in Chinese Familial Breast Cancer Patients withJournal of breast cancer · 2018Article
- Identification of a BRCA2 mutation in a Turkish family with early-onset breast cancer.Clinical case reports · 2018Article
- Estrogen receptor-α promoter methylation is a biomarker for outcome prediction of cisplatin resistance in triple-negative breast cancer.Oncology letters · 2018Article
- CC-115, a dual inhibitor of mTOR kinase and DNA-PK, blocks DNA damage repair pathways and selectively inhibits ATM-deficient cell growthOncotarget · 2017Article
- Potential therapeutic targets of triple-negative breast cancer based on its intrinsic subtype.Oncotarget · 2017Review
- Developmental therapeutics for patients with breast cancer and central nervous system metastasis: current landscape and future perspectives.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Review
- FANCM c.5101C>T mutation associates with breast cancer survival and treatment outcome.International journal of cancer · 2016Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ataxia-telangiectasia-mutated (ATM) kinase is a key transducer of DNA damage signals within the genome maintenance machinery and a tumour suppressor whose germline mutations predispose to familial breast cancer. ATM signalling is constitutively activated in early stages of diverse types of human malignancies and cell culture models in response to oncogene-induced DNA damage providing a barrier against tumour progression. As BRCA1 and BRCA2 are also components of the genome maintenance network and their mutations predispose to breast cancer, we have examined the ATM expression in human breast carcinomas of BRCA1/2 mutation carriers, sporadic cases and familial non-BRCA1/2 patients. Our results show that ATM protein expression is aberrantly reduced more frequently among BRCA1 (33%; P=0.0003) and BRCA2 (30%; P=0.0009) tumours than in non-BRCA1/2 tumours (10.7%). Furthermore, the non-BRCA1/2 tumours with reduced ATM expression were more often estrogen receptor (ER) negative (P=0.0002), progesterone receptor (PR) negative (P=0.004) and were of higher grade (P=0.0004). In our series of 1013 non-BRCA1/2 cases, ATM was more commonly deficient (20%; P=0.0006) and p53 was overabundant (47%; P<0.0000000001) among the difficult-to-treat ER/PR/ERBB2-triple-negative subset of tumours compared with cases that expressed at least one of these receptors (10 and 16% of aberrant ATM and p53, respectively). We propose a model of 'conditional haploinsufficiency' for BRCA1/2 under conditions of enhanced DNA damage in precancerous lesions resulting in more robust activation and hence increased selection for inactivation or loss of ATM in tumours of BRCA1/2 mutation carriers, with implications for genomic instability and curability of diverse subsets of human breast cancer.
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