RESUMO
PURPOSE: Pathogenic/likely pathogenic (P/LP) germline variations in BRCA1 and BRCA2 genes are responsible for the majority of hereditary breast and ovarian cancers. This study presents the BRCA1/BRCA2 sequencing and deletion duplication analyses results of of 493 participants (485 women, 8 men) selected based on the National Comprehensive Cancer Network (NCCN) guidelines. METHODS: Next generation sequencing (NGS) and multiplex ligation-dependent probe amplification methods (MLPA) were used to define germline BRCA1/BRCA2 positivity. RESULTS: Overall, the P/LP frequency of the participants was 17.8%. Five of the likely pathogenic variants were novel. The 5266dupC pathogenic variation, which is a founder mutation in the Ashkenazi Jewish population, was the most common variation among the patients, with a frequency of 5.47%. The pathogenic/likely pathogenic variation frequency was significantly higher (p=0.01) among clinically diagnosed familial cancer patisents than those participants without personal history of cancer but enrolled for BRCA1 testing due to familial risk. BRCA1/BRCA mutation positivity was significantly higher (p=0.000) among those who had at least one first- or second-degree relative with breast/ovarian cancer from patients who had no family history. BRCA1/BRCA2 mutation positivity was 69.23% between the patients who had personal history of both breast and ovarian cancer. CONCLUSION: Based on our findings, we suggest that sequencing all of the coding regions of the BRCA1/BRCA2 genes using NGS is a feasible approach for individuals who are at risk of developing BRCA-related cancer according to NCCN guidelines. The 5266dupC pathogenic variation, as the most common pathogenic variation in the Trakya region of Turkey, should be included if a targeted mutatin screening is planned.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Mama/patologia , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/genética , Detecção Precoce de Câncer/métodos , Feminino , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Linhagem , TurquiaRESUMO
PURPOSE: Efficient and adequate evaluation of therapeutic response in hepatocellular carcinoma (HCC) is an evolving field. We aimed to evaluate apparent diffusion coefficient (ADC) values in the prediction of response to sorafenib and prognosis in patients with advanced HCC. METHODS: Baseline magnetic resonance (MR) imaging was performed before treatment. After sorafenib started, clinical and radiological response were evaluated at approximately 3 months later. ADC measurements were performed by a 12- year experienced radiologist who evaluated MR before and after sorafenib therapy. RESULTS: A total of 17 patients (median age 60 years, range 51-66 and M/F ratio=3.25/1) were analyzed. A significant increase in ADC levels in responders was observed 3 months after sorafenib therapy. Baseline and post-sorafenib ADC values were not significantly associated with mortality (hazard ratio/HR baseline ADC=1.003, p=0.98) and after sorafenib (HR 0.480, p=0.48, respectively). CONCLUSION: Advanced HCC patients with a favorable response to sorafenib had a significant increase in ADC value at the first radiological evaluation. The predictive and prognostic role of ADC for overall survival is still unknown and further research is needed to investigate any possible association.