Targeted massively parallel sequencing of a panel of putative breast cancer susceptibility genes in a large cohort of multiple-case breast and ovarian cancer families
| العنوان: | Targeted massively parallel sequencing of a panel of putative breast cancer susceptibility genes in a large cohort of multiple-case breast and ovarian cancer families |
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| المؤلفون: | Heather Thorne, Bing Jian Feng, Igor V. Makunin, Jonathan Ellis, Melissa C. Southey, kConFab Investigators, Ian G. Campbell, Jun Li, David E. Goldgar, Huong Meeks, Sue Healey, Judy Kirk, David Clouston, Georgia Chenevix-Trench, Gillian Mitchell |
| المصدر: | Journal of Medical Genetics. 53:34-42 |
| بيانات النشر: | BMJ, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Genotype, PALB2, Genes, BRCA2, Genes, BRCA1, Biology, Bioinformatics, Article, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Breast cancer, Biomarkers, Tumor, Odds Ratio, Genetics, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, skin and connective tissue diseases, CHEK2, Genetic Association Studies, Germ-Line Mutation, Genetics (clinical), Genetic testing, Ovarian Neoplasms, Massive parallel sequencing, medicine.diagnostic_test, Computational Biology, High-Throughput Nucleotide Sequencing, Exons, medicine.disease, Pedigree, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Hereditary Breast and Ovarian Cancer Syndrome, Female, Ovarian cancer |
| الوصف: | Gene panel testing for breast cancer susceptibility has become relatively cheap and accessible. However, the breast cancer risks associated with mutations in many genes included in these panels are unknown.We performed custom-designed targeted sequencing covering the coding exons of 17 known and putative breast cancer susceptibility genes in 660 non-BRCA1/2 women with familial breast cancer. Putative deleterious mutations were genotyped in relevant family members to assess co-segregation of each variant with disease. We used maximum likelihood models to estimate the breast cancer risks associated with mutations in each of the genes.We found 31 putative deleterious mutations in 7 known breast cancer susceptibility genes (TP53, PALB2, ATM, CHEK2, CDH1, PTEN and STK11) in 45 cases, and 22 potential deleterious mutations in 31 cases in 8 other genes (BARD1, BRIP1, MRE11, NBN, RAD50, RAD51C, RAD51D and CDK4). The relevant variants were then genotyped in 558 family members. Assuming a constant relative risk of breast cancer across age groups, only variants in CDH1, CHEK2, PALB2 and TP53 showed evidence of a significantly increased risk of breast cancer, with some supportive evidence that mutations in ATM confer moderate risk.Panel testing for these breast cancer families provided additional relevant clinical information for2% of families. We demonstrated that segregation analysis has some potential to help estimate the breast cancer risks associated with mutations in breast cancer susceptibility genes, but very large case-control sequencing studies and/or larger family-based studies will be needed to define the risks more accurately. |
| تدمد: | 1468-6244 0022-2593 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::43d19eaae6d784d350863c11b21f0658Test https://doi.org/10.1136/jmedgenet-2015-103452Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....43d19eaae6d784d350863c11b21f0658 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14686244 00222593 |
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