RESUMO
The deletion of exons 9 to 12 of BRCA1 (9-12 del BRCA1) is considered a founder mutation in the Mexican population. We evaluate the usefulness of the target detection of 9-12 del BRCA1 as the first molecular diagnostic strategy in patients with Hereditary Breast and Ovarian Cancer (HBOC). We performed the genetic assessment of 637 patients with suspected HBOC. The region corresponding to the breakpoints for the 9-12 del BRCA1 was amplified by polymerase chain reaction (PCR). An analysis of the clinical data of the carriers and non-carriers was done, searching for characteristics that correlated with the deletion. The 9-12 del BRCA1 was detected in 5% of patients with suspected HBOC (30/637). In patients diagnosed with ovarian cancer, 13 of 30 were 9-12 del BRCA1 carriers, which represents 43%. We found a significant association between the 9-12 del BRCA1 carriers with triple negative breast cancer and high-grade papillary serous ovarian cancer. We concluded that the detection of the 9-12 del BRCA1 is useful as a first molecular diagnostic strategy in the Mexican population. In particular, it shortens the gap in genetic assessment in patients with triple negative breast cancer and ovarian cancer.
Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Mutação em Linhagem Germinativa , Neoplasias Ovarianas/genética , Adulto , Neoplasias da Mama/diagnóstico , Éxons/genética , Saúde da Família , Feminino , Efeito Fundador , Testes Genéticos , Humanos , México , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Deleção de Sequência , Adulto JovemRESUMO
Dysregulated metabolism is a common feature of cancer cells and is considered a hallmark of cancer. Altered tumor-metabolism confers an adaptive advantage to cancer cells to fulfill the high energetic requirements for the maintenance of high proliferation rates, similarly, reprogramming metabolism confers the ability to grow at low oxygen concentrations and to use alternative carbon sources. These phenomena result from the dysregulated expression of diverse genes, including those encoding microRNAs (miRNAs) which are involved in several metabolic and tumorigenic pathways through its post-transcriptional-regulatory activity. Further, the identification of key actionable altered miRNA has allowed to propose novel targeted therapies to modulated tumor-metabolism. In this review, we discussed the different roles of miRNAs in cancer cell metabolism and novel miRNA-based strategies designed to target the metabolic machinery in human cancer.
