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Start Over Author "T. Wijnen" Publisher public library of science
2 results on '"T. Wijnen"'

1. Exome Sequencing of Germline DNA from Non-BRCA1/2 Familial Breast Cancer Cases Selected on the Basis of aCGH Tumor Profiling

Author

Jeroen F. J. Laros, Nicoline Hoogerbrugge, Petra M. Nederlof, Hans F. A. Vasen, Peter Devilee, Michiel van Galen, Juul T. Wijnen, Christi J. van Asperen, Caro M. Meijers, and Florentine Hilbers

Subjects
Heredity, Genetic Linkage, Genes, BRCA2, Genes, BRCA1, Pathology, Exome, Genome Sequencing, Exome sequencing, Genetics, Comparative Genomic Hybridization, Multidisciplinary, Cancer Risk Factors, Linkage (Genetics), Obstetrics and Gynecology, Genomics, Pedigree, Phenotypes, Oncology, Medicine, Female, Chromosomes, Human, Pair 4, Research Article, Science, Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1], Genotypes, Genetic Causes of Cancer, Breast Neoplasms, Biology, Open Reading Frames, Germline mutation, Breast cancer, Genetic linkage, Diagnostic Medicine, Breast Cancer, medicine, Cancer Genetics, Humans, Family, Allele frequency, Germ-Line Mutation, Hereditary cancer and cancer-related syndromes [ONCOL 1], Genetic heterogeneity, Sequence Analysis, DNA, Comparative Genomics, medicine.disease, Lod Score, Comparative genomic hybridization
Abstract

Contains fulltext : 118406.pdf (Publisher’s version ) (Open Access) The bulk of familial breast cancer risk ( approximately 70%) cannot be explained by mutations in the known predisposition genes, primarily BRCA1 and BRCA2. Underlying genetic heterogeneity in these cases is the probable explanation for the failure of all attempts to identify further high-risk alleles. While exome sequencing of non-BRCA1/2 breast cancer cases is a promising strategy to detect new high-risk genes, rational approaches to the rigorous pre-selection of cases are needed to reduce heterogeneity. We selected six families in which the tumours of multiple cases showed a specific genomic profile on array comparative genomic hybridization (aCGH). Linkage analysis in these families revealed a region on chromosome 4 with a LOD score of 2.49 under homogeneity. We then analysed the germline DNA of two patients from each family using exome sequencing. Initially focusing on the linkage region, no potentially pathogenic variants could be identified in more than one family. Variants outside the linkage region were then analysed, and we detected multiple possibly pathogenic variants in genes that encode DNA integrity maintenance proteins. However, further analysis led to the rejection of all variants due to poor co-segregation or a relatively high allele frequency in a control population. We concluded that using CGH results to focus on a sub-set of families for sequencing analysis did not enable us to identify a common genetic change responsible for the aggregation of breast cancer in these families. Our data also support the emerging view that non-BRCA1/2 hereditary breast cancer families have a very heterogeneous genetic basis.

Published
2013

2. Breast Cancer Risk and 6q22.33: Combined Results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2

Author

Kirchhoff, Tomas, Gaudet, Mia M., Antoniou, Antonis C., McGuffog, Lesley, Humphreys, Manjeet K., Dunning, Alison M., Bojesen, Stig E., Nordestgaard, Borge G., Flyger, Henrik, Kang, Daehee, Yoo, Keun-Young, Noh, Dong-Young, Ahn, Sei-Hyun, Dork, Thilo, Schuermann, Peter, H. Karstens, Johann, Hillemanns, Peter, J. Couch, Fergus, Olson, Janet, Vachon, Celine, Wang, Xianshu, Cox, Angela, Brock, Ian, Elliott, Graeme, W. R. Reed, Malcolm, Burwinkel, Barbara, Meindl, Alfons, Brauch, Hiltrud, Hamann, Ute, Ko, Yon-Dschun, Broeks, Annegien, K. Schmidt, Marjanka, J. Van t Veer, Laura, M. Braaf, Linde, Johnson, Nichola, Fletcher, Olivia, Gibson, Lorna, Peto, Julian, Turnbull, Clare, Seal, Sheila, Renwick, Anthony, Rahman, Nazneen, Wu, Pei-Ei, Yu, Jyh-Cherng, Hsiung, Chia-Ni, Shen, Chen-Yang, C. Southey, Melissa, L. Hopper, John, Hammet, Fleur, Van Dorpe, Thijs, Dieudonne, Anne-Sophie, Hatse, Sigrid, Lambrechts, Diether, L. Andrulis, Irene, Bogdanova, Natalia, Antonenkova, Natalia, I. Rogov, Juri, Prokofieva, Daria, Bermisheva, Marina, Khusnutdinova, Elza, J. van Asperen, Christi, A. E. M. Tollenaar, Robert, J. Hooning, Maartje, Devilee, Peter, Margolin, Sara, Lindblom, Annika, L. Milne, Roger, Ignacio Arias, Jose, Pilar Zamora, M., Benitez, Javier, Severi, Gianluca, Baglietto, Laura, G. Giles, Graham, B. Spurdle, Amanda, Beesley, Jonathan, Chen, Xiaoqing, Holland, Helene, Healey, Sue, Wang-Gohrke, Shan, Chang-Claude, Jenny, Mannermaa, Arto, Kosma, Veli-Matti, Kauppinen, Jaana, Kataja, Vesa, A. Agnarsson, Bjarni, A. Caligo, Maria, K. Godwin, Andrew, Nevanlinna, Heli, Heikkinen, Tuomas, Fredericksen, Zachary, Lindor, Noralane, L. Nathanson, Katherine, M. Domchek, Susan, Loman, Niklas, Karlsson, Per, Stenmark Askmalm, Marie, Melin, Beatrice, von Wachenfeldt, Anna, B. L. Hogervorst, Frans, Verheus, Martijn, A. Rookus, Matti, Seynaeve, Caroline, A. Oldenburg, Rogier, J. Ligtenberg, Marjolijn, G. E. M. Ausems, Margreet, M. Aalfs, Cora, J. P. Gille, Hans, T. Wijnen, Juul, B. Gomez Garcia, Encarna, Peock, Susan, Cook, Margaret, T. Oliver, Clare, Frost, Debra, Luccarini, Craig, Pichert, Gabriella, Davidson, Rosemarie, Chu, Carol, Eccles, Diana, Ong, Kai-Ren, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Gareth Evans, D., Eeles, Rosalind, Gold, Bert, D. P. Pharoah, Paul, Offit, Kenneth, Chenevix-Trench, Georgia, F. Easton, Douglas, Kirchhoff, Tomas, Gaudet, Mia M., Antoniou, Antonis C., McGuffog, Lesley, Humphreys, Manjeet K., Dunning, Alison M., Bojesen, Stig E., Nordestgaard, Borge G., Flyger, Henrik, Kang, Daehee, Yoo, Keun-Young, Noh, Dong-Young, Ahn, Sei-Hyun, Dork, Thilo, Schuermann, Peter, H. Karstens, Johann, Hillemanns, Peter, J. Couch, Fergus, Olson, Janet, Vachon, Celine, Wang, Xianshu, Cox, Angela, Brock, Ian, Elliott, Graeme, W. R. Reed, Malcolm, Burwinkel, Barbara, Meindl, Alfons, Brauch, Hiltrud, Hamann, Ute, Ko, Yon-Dschun, Broeks, Annegien, K. Schmidt, Marjanka, J. Van t Veer, Laura, M. Braaf, Linde, Johnson, Nichola, Fletcher, Olivia, Gibson, Lorna, Peto, Julian, Turnbull, Clare, Seal, Sheila, Renwick, Anthony, Rahman, Nazneen, Wu, Pei-Ei, Yu, Jyh-Cherng, Hsiung, Chia-Ni, Shen, Chen-Yang, C. Southey, Melissa, L. Hopper, John, Hammet, Fleur, Van Dorpe, Thijs, Dieudonne, Anne-Sophie, Hatse, Sigrid, Lambrechts, Diether, L. Andrulis, Irene, Bogdanova, Natalia, Antonenkova, Natalia, I. Rogov, Juri, Prokofieva, Daria, Bermisheva, Marina, Khusnutdinova, Elza, J. van Asperen, Christi, A. E. M. Tollenaar, Robert, J. Hooning, Maartje, Devilee, Peter, Margolin, Sara, Lindblom, Annika, L. Milne, Roger, Ignacio Arias, Jose, Pilar Zamora, M., Benitez, Javier, Severi, Gianluca, Baglietto, Laura, G. Giles, Graham, B. Spurdle, Amanda, Beesley, Jonathan, Chen, Xiaoqing, Holland, Helene, Healey, Sue, Wang-Gohrke, Shan, Chang-Claude, Jenny, Mannermaa, Arto, Kosma, Veli-Matti, Kauppinen, Jaana, Kataja, Vesa, A. Agnarsson, Bjarni, A. Caligo, Maria, K. Godwin, Andrew, Nevanlinna, Heli, Heikkinen, Tuomas, Fredericksen, Zachary, Lindor, Noralane, L. Nathanson, Katherine, M. Domchek, Susan, Loman, Niklas, Karlsson, Per, Stenmark Askmalm, Marie, Melin, Beatrice, von Wachenfeldt, Anna, B. L. Hogervorst, Frans, Verheus, Martijn, A. Rookus, Matti, Seynaeve, Caroline, A. Oldenburg, Rogier, J. Ligtenberg, Marjolijn, G. E. M. Ausems, Margreet, M. Aalfs, Cora, J. P. Gille, Hans, T. Wijnen, Juul, B. Gomez Garcia, Encarna, Peock, Susan, Cook, Margaret, T. Oliver, Clare, Frost, Debra, Luccarini, Craig, Pichert, Gabriella, Davidson, Rosemarie, Chu, Carol, Eccles, Diana, Ong, Kai-Ren, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Gareth Evans, D., Eeles, Rosalind, Gold, Bert, D. P. Pharoah, Paul, Offit, Kenneth, Chenevix-Trench, Georgia, and F. Easton, Douglas

Abstract

Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I-2 = 49.3%; p = less than0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95% CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.

Published
2012
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