Whole-exome sequencing of Finnish hereditary breast cancer families
| Autor: | Minna Kankuri-Tammilehto, Johanna Schleutker, Satu-Leena Laasanen, Anna Lindström, Matti Nykter, Tommi Rantapero, Kirsi Määttä |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Exonucleases Male DNA Repair Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins 0302 clinical medicine Genotype Exome ta318 Genetics (clinical) Exome sequencing Finland Genetics Sanger sequencing Aged 80 and over Ovarian Neoplasms BRCA1 Protein High-Throughput Nucleotide Sequencing Middle Aged BRCA2 Protein Pedigree 030220 oncology & carcinogenesis symbols Female Adult medicine.medical_specialty Breast Neoplasms Biology Article Proto-Oncogene Proteins c-myc 03 medical and health sciences symbols.namesake Breast cancer Molecular genetics Ribonucleotide Reductases medicine Genetic predisposition Humans Genetic Predisposition to Disease Alleles Germ-Line Mutation Aged ta1184 ta1182 medicine.disease ta3122 030104 developmental biology |
| Zdroj: | European Journal of Human Genetics. 25 |
| ISSN: | 1018-4813 |
| DOI: | 10.1038/ejhg.2016.141 |
| Popis: | A remarkable proportion of factors causing genetic predisposition to breast cancer (BC) are unknown in non-BRCA1/2 families. Exome sequencing was performed for 13 high-risk Finnish hereditary breast and/or ovarian cancer (HBOC) families to detect variants contributing to BC susceptibility. After filtering, 18 candidate variants in DNA damage response (DDR) pathway genes were screened in 129 female HBOC patients, up to 989 female controls, and 31 breast tumours by Sanger sequencing/TaqMan assays. In addition, two variants were further studied in 49 male BC patients and 909 male controls. Second, all variants predicted to affect function in six early-onset BC patients were analysed in detail. Variants in ATM, MYC, PLAU, RAD1, and RRM2B were enriched in female HBOC patients compared with controls (odds ratio 1.16-2.16). A rare nonsynonymous variant in RAD50 was detected in a male BC patient. In addition, a very rare BRCA1 variant was identified in a single high-risk family. None of the variants showed wild-type allele loss in breast tumours. Furthermore, novel variants predicted to affect function were detected in early-onset patients in genes, which target DNA repair and replication, signalling, apoptosis, and cell cycle pathways. Family-specific enrichment of multiple DDR pathway gene defects likely explains BC predisposition in the studied families. These findings provide new information on potential BC-related pathways and an excellent premise for future studies. |
| Databáze: | OpenAIRE |
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