ATM germline mutations in Spanish early‐onset breast cancer patients negative for BRCA1/BRCA2 mutations
Abstract
Heterozygous carriers of ATM (ataxia telangiectasia mutated gene) mutations have increased risk of breast cancer (BC). We have estimated the prevalence of mutations in the ATM gene among Spanish patients with early‐onset BC. Forty‐three patients diagnosed with BC before the age of 46 years, and negative for BRCA1 and BRCA2 mutations, were analysed for the presence of ATM mutations. A total of 34 ATM sequence variants were detected: 1 deleterious mutation, 10 unclassified variants and 23 polymorphisms. One patient (2.3%) carried the ATM deleterious mutation (3802delG that causes ataxia telangiectasia in the homozygous state) and 13 patients carried the 10 ATM unclassified variants. The truncating mutation 3802delG and eight of the rare variants were not detected in a control group of 150 individuals. Different bioinformatic sequence analysis tools were used to evaluate the effects of the unclassified ATM changes on RNA splicing and function protein. This in silico analysis predicted that the missense variants 7653 T>C and 8156 G>A could alter the splicing by disrupting an exonic splicing enhancer motif and the 3763 T>G, 6314 G>C, and 8156 G>A variants would affect the ATM protein function. These are the initial results concerning the prevalence of germline mutations in the ATM gene among BC cases in a Spanish population, and they suggest that ATM mutations can confer increased susceptibility to early‐onset BC.
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CHEK2, ATM, NBS1, RAD50, TOPBP1, and RAD51C are mutated in breast cancer patients.
“Correspondingly, these and other genes functioning in the DNA damage response, such as CHEK2, ATM, NBS1, RAD50, TOPBP1 and RAD51C, are mutated in breast cancer patients [12–21].”
From Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1 (2011) · cites this paper as [17]
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Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1
Cantor, S. B., & Guillemette, S. (2011) · Future Oncology · doi:10.2217/fon.10.191 · Cited by 106 · see citing works
“Correspondingly, these and other genes functioning in the DNA damage response, such as CHEK2, ATM, NBS1, RAD50, TOPBP1 and RAD51C, are mutated in breast cancer patients [12–21].”
- Authors
- Brunet, J., Gutiérrez‐Enríquez, S., Torres, A., Bérez, V, Sanjosé, S., Galceran, J., Izquierdo, À., Menéndez, J., Gumà, J., & Borràs, J.
- Affiliations
- Institut Català d'Oncologia (ES)
- Hospital de Sant Pau (ES)
- Universitat Rovira i Virgili (ES)
- Corresponding author
- Brunet, J
- Venue
- Clinical Genetics
- Publisher
- Wiley
- Published
- 2008-04-07
- Volume
- 73
- Issue
- 5
- Pages
- 465-473
- ISSN
- 0009-9163 (ISSN-L)
- 1399-0004
- OpenAlex
- W2111509717
- Cited by
- 21
- References
- 47
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 1 · 2012: 1
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Instituto de Salud Carlos III
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- ATM gene, germline mutations, early-onset breast cancer, truncating mutations, missense mutations, RNA splicing, exonic splicing enhancers, cancer susceptibility, Spanish population
- MeSH terms
- Adult, Breast Neoplasms, DNA-Binding Proteins, Female, Follow-Up Studies, Humans, Protein Serine-Threonine Kinases, Germ-Line Mutation, Cell Cycle Proteins, Genes, BRCA1, Genetic Predisposition to Disease, Genes, BRCA2, Tumor Suppressor Proteins, Ataxia Telangiectasia Mutated Proteins
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