BRCA1 and BRCA2 5′ noncoding region variants identified in breast cancer patients alter promoter activity and protein binding

© 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc. The widespread use of next generation sequencing for clinical testing is detecting an escalating number of variants in noncoding regions of the genome. The clinical significance of the majority of these variants is currently unknown, which presents a significant clinical challenge. We have screened over 6,000 early-onset and/or familial breast cancer (BC) cases collected by the ENIGMA consortium for sequence variants in the 5′ noncoding regions of BC susceptibility genes BRCA1 and BRCA2, and identified 141 rare variants with global minor allele frequency \u3c 0.01, 76 of which have not been reported previously. Bioinformatic analysis identified a set of 21 variants most likely to impact transcriptional regulation, and luciferase reporter assays detected altered promoter activity for four of these variants. Electrophoretic mobility shift assays demonstrated that three of these altered the binding of proteins to the respective BRCA1 or BRCA2 promoter regions, including NFYA binding to BRCA1:c.-287C\u3eT and PAX5 binding to BRCA2:c.-296C\u3eT. Clinical classification of variants affecting promoter activity, using existing prediction models, found no evidence to suggest that these variants confer a high risk of disease. Further studies are required to determine if such variation may be associated with a moderate or low risk of BC

Effect of laser beam treatment on the structure of oxides formed on the surface of NiCrAlY powder

Translated from Russian (Proccedings of Advanced Materials '99, Kiev)SIGLEAvailable from British Library Document Supply Centre-DSC:9023.190(10489)T / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Effect of laser beam treatment on the structure of oxides formed on the surface of NiCrAlY powder

Translated from Slovak (Advanced materials - properties and application, Technical Univ. Kosice, Slovakia, 2000)SIGLEAvailable from British Library Document Supply Centre-DSC:9023.190(10337)T / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Structure of NiCrAlY metal powders plasma sprayed and captured in water

Translated from Slovak (Report of the Inst. of Materials and Machine Mechanics, Slovak Academy of Sciences, Bratislava, 1997)SIGLEAvailable from British Library Document Supply Centre-DSC:9023.190(VR-Trans--8685)T / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Examination of the structure of oxides formed on the surface of NiCrAlY powder after laser beam treatment

Translated from Czech (Kovove Mater. 1998 (2) p. 87-95)SIGLEAvailable from British Library Document Supply Centre-DSC:9023.190(VR-Trans--8831)T / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Structure of NiCrAlY metal powders

Translated from Czech (Kovove Mater. 1997 (3) p. 188-193)SIGLEAvailable from British Library Document Supply Centre-DSC:9023.190(VR-Trans--8659)T / BLDSC - British Library Document Supply CentreGBUnited Kingdo