RESUMO
About 5-10% of all ovarian cancer cases show familial clustering, and some 15-25% of familial ovarian cancer cases are mediated by high-penetrance mutations in the BRCA1 and BRCA2 genes. Only few other genes have been identified for familial ovarian cancer.We conducted targeted next-generation sequencing of the protein coding region of 21 candidate genes, including UTR regions, in genomic DNA samples of 48 patients with familial ovarian cancer from the Republic of Bashkortostan. We identified deleterious variants in BRCA1, BRCA2, CHEK2, MSH6 and NBN in a total of 16 patients (33%). The NBN truncating variant, p.W143X, had not previously been reported. Seven patients (15%) were carriers of the c.5266dupC variant in BRCA1, supporting a Russian origin of this founder allele. An additional 15 variants of uncertain clinical significance were observed. We conclude that our gene panel explains about one-third of familial ovarian cancer risk in the Republic of Bashkortostan.
Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Humanos , Feminino , Bashkiria , Proteína BRCA1/genética , Genes BRCA2 , Mutação , Neoplasias Ovarianas/genética , Carcinoma Epitelial do Ovário/genética , Sequenciamento de Nucleotídeos em Larga Escala , Predisposição Genética para Doença , Neoplasias da Mama/genéticaRESUMO
Carbon tetrachloride is a well-studied hepatotropic poison. Animal models of exposure to carbon tetrachloride resemble acute liver damage in humans. This paper presents the study of the expression of genes related to cell cycle control, apoptosis, and oxidative stress in a model of carbon tetrachloride-induced toxic hepatitis in rats. White mongrel male rats were injected with a 50% oil solution of carbon tetrachloride at a dose of 0.125-4.000 g/kg (experimental group) or olive oil (control group). The animals were decapitated 24 and 72 h after the administration of carbon tetrachloride, and the qRT-PCR expression levels of the genes encoding hemoxygenase-1 (Hmox1), cell cycle checkpoint kinase-1 (Chek1), and caspase-7 (Casp7) in the liver were analyzed. The increase in the expression levels of Hmox1 and Chek1 after exposure was detected. These genes may either play a role in promoting pathological oxidative stress in the liver or be a part of a stress response. We have concluded that the major pathway of the liver damage in carbon tetrachloride exposed animals is necrosis rather than apoptosis.
