RESUMO
La Ataxia-Telangiectasia (AT) es una rara enfermedad de herencia autosómica recesiva y de afección multisistémica, caracterizada por ataxia progresiva, inmunodeficiencia variable con infecciones recurrentes, riesgo incrementado de neoplasias con o sin telangiectasias óculo-cutáneas. La AT es causada por variantes patogénicas bialélicas en el gen ATM. Su diagnóstico se basa en la sospecha de un cuadro clínico compatible, niveles elevados de alfafetoproteína, atrofia cerebelosa y estudios genéticos. No existe tratamiento curativo de AT y su manejo se basa en medidas de soporte y prevención de complicaciones y asesoramiento genético. En esta revisión, actualizamos la epidemiología, manifestaciones clínicas, diagnóstico y tratamiento de AT incluyendo una búsqueda de casos publicados en el Perú.
Ataxia-Telangiectasia (AT) is a rare autosomal recessive disease with multisystemic involvement, characterized by slowly progressive ataxia, variable immunodeficiency with recurrent infections, increased risk of neoplasms with or without oculocutaneous telangiectasias. AT is caused by biallelic pathogenic variants within the ATM gene. Its diagnosis is based on suspicion of a compatible clinical symptomatology, increased levels of alpha-fetoprotein, cerebellar atrophy, and genetic testing. There is no curative treatment for AT and its management is based on supportive and preventive measures of eventual complications and genetic counseling. This review updates the epidemiology, clinical manifestations, diagnosis, and treatment of AT, including a search for cases published in Peru.
Assuntos
Humanos , Peru , Ataxia , Sinais e Sintomas , Ataxia Telangiectasia , Epidemiologia , Proteínas Mutadas de Ataxia TelangiectasiaRESUMO
Objective:To analyze the relationship between ataxia telangiectasia mutated (ATM) single nucleotide polymorphism (SNP) at rs1801516 and rs1800054 and sporadic breast cancer (SBC) in Inner Mongolia.Methods:A total of 102 patients with SBC (72 Han and 30 Mongolian) who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2018 to September 2019 were prospectively collected as case group and 102 healthy women (72 Han and 30 Mongolian) during the same period as control group. 2 ml of venous blood was collected to extract DNA. According to the Single Nucleotide Polymorphism Database (dbSNP), the highly polymorphic sites rs1801516 and rs1800054 of ATM gene were selected. The polymerase chain reaction (PCR) and direct sequencing were used to detect the polymorphism of the two sites, and the correlation between the single nucleotide polymorphism of the two sites and the susceptibility of SBC in Inner Mongolia was analyzed. The potential association between clinicopathological factors and ATM gene polymorphism in patients with SBC in Inner Mongolia were explored.Results:GG, GA and AA genotypes were detected in rs1801516 locus of ATM gene. Only CC genotype was detected in the rs1800054 locus of ATM gene. There was no significant difference in the distribution of genotype frequency and allele frequency between Mongolian breast cancer group and Han breast cancer group, Mongolian control group and Han control group, Mongolian breast cancer group and Mongolian control group, Han breast cancer group and Han control group (all P>0.05). Logistic regression analysis showed that allele G was the susceptibility gene of SBC in Inner Mongolia ( OR: 1.775, 95% CI: 1.04-3.03, P=0.04). ATM rs1801516 polymorphism may be associated with increased risk of breast cancer in patients with mass diameter ≤2 cm and/or without lymph node metastasis (all P<0.05). Conclusions:The polymorphism of ATM gene rs1801516 and rs1800054 may not be significantly correlated with the risk of SBC in Inner Mongolia. The rs1801516 locus may be associated with increased risk of breast cancer in patients with mass diameter ≤2 cm and/or without lymph node metastasis. Gene G may be one of the susceptible genes of SBC in Inner Mongolia.
RESUMO
Objective: To investigate the effects of ataxia-telangiectasia mutated (ATM) gene-silencing on the proliferation, migration and invasion of human triple-negative breast cancer MDA-MB-231 cells. Methods: The recombinant lentiviral vectors with ATM gene-targeted specific shRNA or the negative control sequence (as the negative control group) were infected into the human triple-negative breast cancer MDA-MB-231 cells to obtain the ATM gene-silencing cells. At the same time, the uninfected MDA-MB-231 cells was used as the blank control group. After screening by puromycin, the infection efficiency of each group was observed under a fluorescence microscope. The expressions of ATM mRNA and protein in MDA-MB-231 cells in the three groups were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The effects of ATM gene-silencing on proliferation, cycle distribution, migration and invasion of MDA-MB-231 cells were analyzed by MTT method, FCM, cell wound healing assay and Transwell assays, respectively. Results: The human triple-negative breast cancer MDA-MB-231 cells with stable ATM genesilencing were established successfully. Compared with the blank control and negative control groups, the proliferation and cell cycle distribution of MDA-MB-231 cells in ATM gene-silencing group had no significant change (all P > 0.05), but the migration and invasion abilities of MDA-MB-231 cells in ATM gene-silencing group were decreased significantly (all P<0.05). Conclusion: The down-regulation of ATM gene expression can significantly inhibit the migration and invasion of human triple-negative breast cancer MDA-MB-231 cells.
