The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
The Landscape of Somatic Genetic Alterations in Breast Cancers From ATM Germline Mutation Carriers
Open accessAbstract
Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53 mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATM variants and TP53 somatic mutations are mutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-related mutational signatures, and that TP53 and ATM genetic alterations are likely epistatic.
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“Despite the role of TP53, ATM and CHEK2 in DNA-damage signalling and double-strand breaks detection, these tumours do not show evidence of BRCA-deficient signatures, as previously described [9, 13, 19], but instead they harbour highly complex clustered chromosomal rearrangements.”
From Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers (2019) · cites this paper as [19]
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Citations
Cites
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“6),(17) using copy number information defined using FACETS,(18) as previously described.(13,14) Total RNA extracted from the 2 different components was subjected to paired-end RNA sequencing (2× 50 bp cycles) at MSKCC’s IGO, as previously described.”
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Genetic characteristics of platinum-sensitive ovarian clear cell carcinomaPreprint
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“In this context, screening for these mutations provides a significant advantage for clinical genetic testing and genetic counseling in women at risk for BC [14, 15].”
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BackgroundOzato, T., Kono, Y., Horiguchi, S., Tsutsumi, K., Yamamoto, H., Hirasawa, A., Ennishi, D., Tomida, S., Toyooka, S., & Otsuka, M. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5132243
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Next-Generation Sequence (NGS) Analysis: Current Trends, Techniques, and Applications
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“60,61 60-62 These findings suggest that these genes may be epistatic with TP53 , with potential functional redundancy.”
Self-citationVecchione, A., & Bargiacchi, L. (2026) · Current clinical pathology · doi:10.1007/978-3-032-18790-1_11
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“As a result, these alterations do not uniformly confer true homologous recombination deficiency [18,21,22].”
Exploiting the weak link: Ataxia-Telangiectasia Mutated dysfunction in oesophagogastric tumours
Trybala, Z., Costella, G., Bednarova, K., Arcimowicz, Ł., Aigner, A. M., Lordick, F., Obermannova, R. L., & Müller, P. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2026.105503
Breast–Ovarian Hereditary Cancer Syndrome: Beyond BRCA1 and BRCA2
Имянитов, Е. Н., & Соколенко, А. П. (2026) · Current Oncology · doi:10.3390/curroncol33090556
Doad, B. S., Borges, G. D. O., Zhao, Y., Laurent, D., Lees‐Miller, S. P., Murguía-Favela, L. E., Grunebaum, E., & Narendran, A. (2026) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-026-09205-y
“However, the immunologic phenotype likely depends on tumor type, ATM loss-of-function (LOF) definition, and therapeutic context [ 34, 35].”
Metadata
- Authors
- Weigelt, B., Bi, R., Kumar, R., Blecua, P., Mandelker, D. L., Geyer, F. C., Pareja, F., James, P. A., kConFab Investigators, Couch, F. J., Eccles, D. M., Blows, F., Pharoah, P., Li, A., Selenica, P., Lim, R. S., Jayakumaran, G., Waddell, N., Shen, R., Norton, L., Wen, H. Y., Powell, S. N., Riaz, N., Robson, M. E., Reis-Filho, J. S., & Chenevix-Trench, G.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Peter MacCallum Cancer Centre (AU)
- Mayo Clinic (US)
- University of Cambridge (GB)
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia (NW, GCT)
- Corresponding author
- Reis-Filho, Jorge S
- ORCID
- Weigelt, Britta
- Bi, Rui
- Kumar, Rahul
- Blecua, Pedro
- Mandelker, Diana L
- Geyer, Felipe C
- Pareja, Fresia
- James, Paul A
- Couch, Fergus J
- Eccles, Diana M
- Pharoah, Paul
- Li, Anqi
- Selenica, Pier
- Lim, Raymond S
- Jayakumaran, Gowtham
- Shen, Ronglai
- Norton, Larry
- Wen, Hannah Y
- Powell, Simon N
- Riaz, Nadeem
- Robson, Mark E
- Reis-Filho, Jorge S
- Venue
- JNCI: Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-02-28
- Volume
- 110
- Issue
- 9
- Pages
- 1030-1034
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- PMC
- PMC6136925
- OpenAlex
- W2792571019
- Cited by
- 128
- References
- 22
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 13 · 2023: 17 · 2022: 16 · 2021: 19 · 2020: 21 · 2019: 18 · 2018: 4
- FWCI
- 9.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Meredith Israel Thomas Fund
- Breast Cancer Research Foundation
- National Institutes of Health
- National Cancer Institute (P30CA008748)
- NIH (CA192393, CA176785)
- National Health and Medical Research Council of Australia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- breast cancer, somatic alterations, loss of heterozygosity, TP53 mutation, epistasis, hormone receptor-positive breast cancer, tumor immune infiltrate, DNA damage response
- MeSH terms
- Exome Sequencing, Adult, Aged, Breast Neoplasms, Female, Heterozygote, Humans, Middle Aged, Mutation, Biomarkers, Tumor, Germ-Line Mutation, Genetic Predisposition to Disease, Genomics, Genetic Association Studies, Ataxia Telangiectasia Mutated Proteins
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