title: Structure-based assessment of BRCA1 and BRCA2 mutations in a small Spanish population.
abstract: Breast cancer is the most frequent cancer type among women in the world. There is abundant evidence, that alterations in the breast cancer susceptibility genes, BRCA1 and BRCA2, are present in a large proportion of families with multiple cases of breast and ovarian cancer. Our aim was to better understand the molecular and structural insights associated with the most frequent alterations, found in the BRCA1 and BRCA2 genes, within our patients. We analyzed 50 breast cancer cases. Of those, 24% were found to carry deleterious mutations, and up to 10 rare variants of unknown significance were detected. The frequency of polymorphic changes was considerably different between genes, BRCA1 (55%) and BRCA2 (19.4%). By looking at the protein level, the changes observed within the BRCA1 and BRCA2 genes could affect not only the nucleic location of the protein but also disrupt the folding and, therefore, the tumor suppressor function.
authors.affiliation: Laboratory of Biotechnology, University Clinic of Navarra, Avda. Pio XII 36, 31008 Pamplona, Navarra, Spain. jsalgadog@unav.es
authors.forename: J
authors.initials: J
authors.lastname: Salgado
authors.forename: N
authors.initials: N
authors.lastname: Zabalegui
authors.forename: F
authors.initials: F
authors.lastname: García-Amigot
authors.forename: M C
authors.initials: MC
authors.lastname: Gil
authors.forename: M S
authors.initials: MS
authors.lastname: González
authors.forename: J
authors.initials: J
authors.lastname: García-Foncillas
mesh_terms: D019313:BRCA1 Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D024682:BRCA2 Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D005260:Female; D005796:Genes / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009154:Mutation; D011485:Protein Binding / Q000235:genetics; D017510:Protein Folding; D021381:Protein Transport / Q000235:genetics; D013030:Spain
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein