Evaluation of the contribution of the three breast cancer susceptibility genes CHEK2, STK11, and PALB2 in non-BRCA1/2 French Canadian families with high risk of breast cancer
| Autor: | Francine Durocher, Yvan Labrie, Christopher St-Laurent Pedneault, Frédéric Guénard, Geneviève Ouellette, Jacques Simard |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Adult
Risk Canada PALB2 DNA Mutational Analysis Genes BRCA2 STK11 Genes BRCA1 Breast Neoplasms Biology Protein Serine-Threonine Kinases medicine.disease_cause Breast cancer susceptibility genes Breast cancer AMP-Activated Protein Kinase Kinases medicine Humans Family Genetic Predisposition to Disease skin and connective tissue diseases Gene CHEK2 Genetics (clinical) Aged Genetics Mutation Tumor Suppressor Proteins Carcinoma Quebec Nuclear Proteins General Medicine Middle Aged medicine.disease Checkpoint Kinase 2 French canadian Cancer research Female Fanconi Anemia Complementation Group N Protein |
| Zdroj: | Genetic testing and molecular biomarkers. 14(4) |
| ISSN: | 1945-0257 |
| Popis: | Inactivating mutations of the CHEK2 and STK11 genes are responsible for Li-Fraumeni and Peutz-Jeghers syndrome, respectively, both autosomal dominant syndromes associated with an increased risk of breast cancer. The PALB2/FANCN gene encodes a nuclear partner of BRCA2 and acts as a linker between BRCA1 and BRCA2. Monoallelic PALB2 truncating mutations were shown to confer higher risk of breast cancer. To evaluate the proportion of French Canadian non-BRCA1/BRCA2 families with high risk of breast cancer potentially harboring alterations in these three breast cancer susceptibility genes, the whole coding and flanking intronic sequences were analyzed in a series of 96 high-risk breast cancer individuals. Despite no PALB2 deleterious truncating mutations being identified, the c.1100delC breast-cancer-associated CHEK2 mutation and a STK11 mutation reported to be the causative mutation in a Peutz-Jeghers family were identified. This extensive analysis also led to the identification of several variants in these genes. Ascertainment of allele frequency of these variants in a cohort of 96 healthy unrelated women suggests a difference in allele frequency for two STK11 intronic variants. In addition, large genomic rearrangements in both STK11 and PALB2 were also examined. Our analysis led to the conclusion that CHEK2, STK11, and PALB2 mutations or large genomic rearrangements of either STK11 or PALB2 are rare, and do not contribute to a substantial fraction of breast cancer susceptibility in high-risk French Canadian breast cancer families. |
| Databáze: | OpenAIRE |
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