Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations
Language English Country Netherlands Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Checkpoint Kinase 2 MeSH
- Carcinoma, Ductal, Breast epidemiology genetics pathology MeSH
- Genetic Predisposition to Disease * MeSH
- Incidence MeSH
- Carcinoma, Intraductal, Noninfiltrating epidemiology genetics pathology MeSH
- Humans MeSH
- Carcinoma, Lobular genetics pathology MeSH
- Mutation, Missense genetics MeSH
- Breast Neoplasms genetics pathology MeSH
- Prognosis MeSH
- Protein Serine-Threonine Kinases genetics MeSH
- Case-Control Studies MeSH
- Protein Structure, Tertiary MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- Checkpoint Kinase 2 MeSH
- CHEK2 protein, human MeSH Browser
- Protein Serine-Threonine Kinases MeSH
The CHEK2 gene mutations I157T (c.470T>C) and IVS2+1G>A affecting the forkhead-associated domain (FHA) have been shown to increase the risk of breast cancer development in several populations. We analyzed the CHEK2 gene segment coding for FHA domain in 673 unselected breast cancer patients and 683 controls from the Czech Republic using the denaturant high-performance liquid chromatography. The found frequency of predominant FHA alteration I157T did not differ between breast cancer patients (19/673; 2.82%) and controls (17/683; 2.49%; P=0.71). Besides this mutation we characterized another nine alterations-six located within FHA coding sequence and three occurring in introns 1 or 2). Eight variants occurred once each in patients with breast cancer and two were present in controls. Three alterations found in breast cancer patients were novel missense variants (Y159H, T172A, and L174F) affecting highly conservative residues in FHA domain. Despite the lack of association of I157T mutation with breast cancer development in our population we deduced that the FHA domain is the subject of rare population-specific alterations that might modify risk of various cancers.
References provided by Crossref.org
CHEK2 Germline Variants in Cancer Predisposition: Stalemate Rather than Checkmate
Association of Germline CHEK2 Gene Variants with Risk and Prognosis of Non-Hodgkin Lymphoma
