Copy Number Variation Analysis in Familial BRCA1/2-Negative Finnish Breast and Ovarian Cancer
| Autor: | Minna Kankuri-Tammilehto, Oyediran Akinrinade, Johanna Schleutker, Mauno Vihinen, Satu-Leena Laasanen, Kirsi M. Kuusisto |
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| Přispěvatelé: | Biolääketieteellisen teknologian yksikkö - Institute of Biomedical Technology, University of Tampere |
| Rok vydání: | 2013 |
| Předmět: |
Heredity
Genes BRCA2 Genes BRCA1 Genome-wide association study 0302 clinical medicine Lääketieteen bioteknologia - Medical biotechnology Gene Duplication ta318 Copy-number variation Finland Genetics 0303 health sciences Multidisciplinary Obstetrics and Gynecology Middle Aged Ovarian Cancer Pedigree 3. Good health Oncology 030220 oncology & carcinogenesis Cytogenetic Analysis Medicine Hereditary Breast and Ovarian Cancer Syndrome Medical genetics Female Medical Genetics Cancer Screening Research Article SNP array Adult medicine.medical_specialty DNA Copy Number Variations Science Genetic counseling Genetic Counseling Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide White People Cytogenetics Young Adult 03 medical and health sciences Breast cancer Germline mutation Syöpätaudit - Cancers Breast Cancer Cancer Genetics Cancer Detection and Diagnosis medicine Humans Genetic Predisposition to Disease Genetic Testing Germ-Line Mutation Aged 030304 developmental biology Complex Traits ta1184 ta1182 Cancers and Neoplasms Reproducibility of Results Human Genetics ta3122 medicine.disease Case-Control Studies Genetics of Disease Gynecological Tumors Gene Deletion Genome-Wide Association Study |
| Zdroj: | PLoS ONE PLoS ONE; 8(8), no e71802 (2013) PLoS ONE, Vol 8, Iss 8, p e71802 (2013) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0071802 |
| Popis: | Background Inherited factors predisposing individuals to breast and ovarian cancer are largely unidentified in a majority of families with hereditary breast and ovarian cancer (HBOC). We aimed to identify germline copy number variations (CNVs) contributing to HBOC susceptibility in the Finnish population. Methods A cohort of 84 HBOC individuals (negative for BRCA1/2-founder mutations and pre-screened for the most common breast cancer genes) and 36 healthy controls were analysed with a genome-wide SNP array. CNV-affecting genes were further studied by Gene Ontology term enrichment, pathway analyses, and database searches to reveal genes with potential for breast and ovarian cancer predisposition. CNVs that were considered to be important were validated and genotyped in 20 additional HBOC individuals (6 CNVs) and in additional healthy controls (5 CNVs) by qPCR. Results An intronic deletion in the EPHA3 receptor tyrosine kinase was enriched in HBOC individuals (12 of 101, 11.9%) compared with controls (27 of 432, 6.3%) (OR = 1.96; P = 0.055). EPHA3 was identified in several enriched molecular functions including receptor activity. Both a novel intronic deletion in the CSMD1 tumor suppressor gene and a homozygous intergenic deletion at 5q15 were identified in 1 of 101 (1.0%) HBOC individuals but were very rare (1 of 436, 0.2% and 1 of 899, 0.1%, respectively) in healthy controls suggesting that these variants confer disease susceptibility. Conclusion This study reveals new information regarding the germline CNVs that likely contribute to HBOC susceptibility in Finland. This information may be used to facilitate the genetic counselling of HBOC individuals but the preliminary results warrant additional studies of a larger study group Public Library of Science open access |
| Databáze: | OpenAIRE |
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