Spectrum and characterisation of BRCA1 and BRCA2 deleterious mutations in high-risk Czech patients with breast and/or ovarian cancer

<p>Abstract</p> <p>Background</p> <p>The incidence of breast cancer has doubled over the past 20 years in the Czech Republic. Hereditary factors may be a cause of young onset, bilateral breast or ovarian cancer, and familial accumulation of the disease. <it>BRCA1 </it>and <it>BRCA2 </it>mutations account for an important fraction of hereditary breast and ovarian cancer cases. One thousand and ten unrelated high-risk probands with breast and/or ovarian cancer were analysed for the presence of a <it>BRCA1 </it>or <it>BRCA2 </it>gene mutation at the Masaryk Memorial Cancer Institute (Czech Republic) during 1999–2006.</p> <p>Methods</p> <p>The complete coding sequences and splice sites of both genes were screened, and the presence of large intragenic rearrangements in <it>BRCA1 </it>was verified. Putative splice-site variants were analysed at the cDNA level for their potential to alter mRNA splicing.</p> <p>Results</p> <p>In 294 unrelated families (29.1% of the 1,010 probands) pathogenic mutations were identified, with 44 different <it>BRCA1 </it>mutations and 41 different <it>BRCA2 </it>mutations being detected in 204 and 90 unrelated families, respectively. In total, three <it>BRCA1 </it>founder mutations (c.5266dupC; c.3700_3704del5; p.Cys61Gly) and two <it>BRCA2 </it>founder mutations (c.7913_7917del5; c.8537_8538del2) represent 52% of all detected mutations in Czech high-risk probands. Nine putative splice-site variants were evaluated at the cDNA level. Three splice-site variants in <it>BRCA1 </it>(c.302-3C>G; c.4185G>A and c.4675+1G>A) and six splice-site variants in <it>BRCA2 </it>(c.475G>A; c.476-2>G; c.7007G>A; c.8755-1G>A; c.9117+2T>A and c.9118-2A>G) were demonstrated to result in aberrant transcripts and are considered as deleterious mutations.</p> <p>Conclusion</p> <p>This study represents an evaluation of deleterious genetic variants in the <it>BRCA1 </it>and <it>2 </it>genes in the Czech population. The classification of several splice-site variants as true pathogenic mutations may prove useful for genetic counselling of families with high risk of breast and ovarian cancer.</p

Chemical bonds and elemental compositions of BCxNy layers produced by chemical vapor deposition with trimethylamine borane, triethylamine borane, or trimethylborazine

BCxNy films were produced from single-source precursors in a chemical vapor deposition process. The boranes were introduced as precursors at low pressure conditions and at a temperature of 700 °C, whereas the borazine was handled at 400 °C and with a plasma enhancement at an electrical power input of 40 W. Additionally, as inert or reactive gases, H2, He, N2, and NH3, respectively, were used. The films deposited on Si(100) substrates were chemically characterized by X-ray photoelectron spectroscopy and by synchrotron radiation-based total-reflection X-ray fluorescence combined with near-edge X-ray absorption fine structure and quantified elementally by energy-dispersive X-ray spectroscopy. The results are critically compared. With the application of boranes without NH3, compounds with a dominating carbidic character were identified, whereas with the addition of NH3 to the boranes, a nitridic character was prevalent. In case of using borazine for the synthesis, the nitridic character was found at the application of all auxiliary gases. For both groups stoichiometric formulas derived from energy-dispersive X-ray spectroscopy are proposed: B3.5–4C4N2–2.5 for the carbidic region and B3.5C1.5N5 for the nitridic region