Mutation analysis of the CHK2 gene in breast carcinoma and other cancers
Open accessAbstract
BACKGROUND: Mutations in the CHK2 gene at chromosome 22q12.1 have been reported in families with Li-Fraumeni syndrome. Chk2 is an effector kinase that is activated in response to DNA damage and is involved in cell-cycle pathways and p53 pathways. METHODS: We screened 139 breast tumors for loss of heterozygosity at chromosome 22q, using seven microsatellite markers, and screened 119 breast tumors with single-strand conformation polymorphism and DNA sequencing for mutations in the CHK2 gene. RESULTS: Seventy-four of 139 sporadic breast tumors (53%) show loss of heterozygosity with at least one marker. These samples and 45 tumors from individuals carrying the BRCA2 999del5 mutation were screened for mutations in the CHK2 gene. In addition to putative polymorphic regions in short mononucleotide repeats in a non-coding exon and intron 2, a germ line variant (T59K) in the first coding exon was detected. On screening 1172 cancer patients for the T59K sequence variant, it was detected in a total of four breast-cancer patients, two colon-cancer patients, one stomach-cancer patient and one ovary-cancer patient, but not in 452 healthy individuals. A tumor-specific 5' splice site mutation at site +3 in intron 8 (TTgt [a --> c]atg) was also detected. CONCLUSION: We conclude that somatic CHK2 mutations are rare in breast cancer, but our results suggest a tumor suppressor function for CHK2 in a small proportion of breast tumors. Furthermore, our results suggest that the T59K CHK2 sequence variant is a low-penetrance allele with respect to tumor growth.
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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 [13]
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- Authors
- Ingvarsson, S., Sigbjornsdottir, B. I., Huiping, C., Hafsteinsdottir, S. H., Ragnarsson, G., Barkardottir, R. B., Arason, A., Egilsson, V., & Bergthorsson, J. T.
- Venue
- Breast Cancer Research
- Published
- 2002-06-01
- Volume
- 4
- Issue
- 3
- Pages
- R4-R4
- ISSN
- 1465-5411 (ISSN-L)
- 1465-542X
- PMC
- PMC111029
- OpenAlex
- W1581390152
- Cited by
- 63
- References
- 24
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 4 · 2016: 1 · 2014: 1 · 2013: 4 · 2012: 3
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Breast Cancer Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Skemman (submittedVersion)
- Funders
- Háskóli Íslands
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- breast cancer, somatic mutations, loss of heterozygosity, tumor suppressor, 5' splice site mutation, low-penetrance alleles, colon cancer, gastric cancer, ovarian cancer
- MeSH terms
- Adult, Breast Neoplasms, Chromosomes, Human, Pair 22, Colonic Neoplasms, Female, Heterozygote, Humans, Male, Middle Aged, Mutation, Ovarian Neoplasms, Polymorphism, Genetic, Protein Kinases, Stomach Neoplasms, Thyroid Neoplasms, Protein Serine-Threonine Kinases, Point Mutation, Loss of Heterozygosity, Genes, BRCA2, Checkpoint Kinase 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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