RESUMO
Gene-panel sequencing allows comprehensive analysis of multiple genes simultaneously and is now routinely used in clinical mutation testing of high-risk breast and ovarian cancer patients. However, only BRCA1 and BRCA2 are often analyzed also for large genomic changes. Here, we have analyzed 10 clinically relevant susceptibility genes in 95 breast or ovarian cancer patients with gene-panel sequencing including also copy number variants (CNV) analysis for genomic changes. We identified 12 different pathogenic BRCA1, BRCA2, TP53, PTEN, CHEK2, or RAD51C mutations in 18 of 95 patients (19%). BRCA1/2 mutations were observed in 8 patients (8.4%) and CHEK2 protein-truncating mutations in 7 patients (7.4%). In addition, we identified a novel duplication encompassing most of the RAD51C gene. We further genotyped the duplication in breast or ovarian cancer families (n = 1149), in unselected breast (n = 1729) and ovarian cancer cohorts (n = 553), and in population controls (n = 1273). Seven additional duplication carries were observed among cases but none among controls. The duplication associated with ovarian cancer risk (3/590 of all ovarian cancer patients, 0.5%, P = .032 compared with controls) and was found to represent a large fraction of all identified RAD51C mutations in the Finnish population. Our data emphasizes the importance of comprehensive mutation analysis including CNV detection in all the relevant genes.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Proteínas de Ligação a DNA/genética , Duplicação Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Adulto , Idoso , Alelos , Biomarcadores Tumorais , Éxons , Feminino , Finlândia , Frequência do Gene , Estudos de Associação Genética/métodos , Testes Genéticos , Mutação em Linhagem Germinativa , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-IdadeRESUMO
The biotype of the citrus nematode (Tylenchulus semipenetrans) from Zebediela and Champagne Citrus Estates, Republic of South Africa, was determined using 2-year-old differential hosts, namely, grape (Vitis vinifera cv. Richter 110), carrizo citrange (Citrus sinensis × Poncirus trifoliata), rough lemon (C. jambhiri), olive (Olea europaea cv. Misson), and trifoliate orange (P. trifoliata). The study was conducted under greenhouse conditions with 10 replicates. Nematodes from Zebediela and Champagne were extracted from roots through mechanical shaking, sieving, and incubation in Baermann trays and inoculated at 10,000 and 40,000 eggs and juveniles per plant, respectively. Results demonstrated that the citrus nematode from Zebediela had reproductive factors greater than one on grape, rough lemon, trifoliate orange, and carrizo citrange, but lower than one on olive. Reproductive factors were less than one for all differential hosts with the Champagne population, with olive having the lowest value. Differential-host tests using Zebediela and Champagne nematode populations suggested that the T. semipenetrans biotype is poncirus.