RESUMEN
Penile cancer is a rare neoplasm that seems to be linked to socio-economic differences. Mitochondrial genome alterations are common in many tumors types and are reported as regulating oxidative metabolism and impacting tumorigenesis. In this study, we evaluate for the first time the mitochondrial genome in penile carcinoma (PeCa), aiming to evaluate heteroplasmy, mitochondrial DNA (mtDNA) mutational load and mtDNA content in Penile tumors. Using next generation sequencing (NGS), we sequenced the mitochondrial genome of 13 penile tumors and 12 non-neoplastic tissue samples, which allowed us to identify mtDNA variants and heteroplasmy. We further evaluated variant's pathogenicity using Mutpred predictive software and calculated mtDNA content using quantitative PCR. Mitochondrial genome sequencing revealed an increase number of non-synonymous variants in the tumor tissue, along with higher frequency of heteroplasmy and mtDNA depletion in penile tumors, suggesting an increased mitochondrial instability in penile tumors. We also described a list of mitochondrial variants found in penile tumor and normal tissue, including five novel variants found in the tumoral tissue. Our results showed an increased mitochondrial genome instability in penile tumors. We also suggest that mitochondrial DNA copy number (mtDNAcn) and mtDNA variants may act together to imbalance mitochondrial function in PeCa. The better understanding of mitochondrial biology can bring new insights on mechanisms and open a new field for therapy in PeCa.
Asunto(s)
Mitocondrias/genética , Neoplasias del Pene/genética , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Variaciones en el Número de Copia de ADN/genética , ADN Mitocondrial/genética , Variación Genética/genética , Genoma/genética , Genoma Mitocondrial/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Análisis de Secuencia de ADN/métodosRESUMEN
A produção de força muscular pode estar comprometida em pacientes portadores de miopatias. Estas representam um grupo heterogêneo de doenças com distintas características clínicas e morfológicas. Supõe-se que achados de desempenho funcional estejam relacionados com o tipo predominante de fibra expresso no músculo em análise. OBJETIVO: Correlacionar a proporção das fibras tipo 2 (FT2) do músculo bíceps braquial de sujeitos com hipótese clínica de miopatia (HCM) com picos de torque isométrico e isocinético de flexão do cotovelo. MATERIAIS E MÉTODOS: Participaram deste estudo sete sujeitos com HCM: quatro do sexo feminino com média de idade de 37 anos (dp= 9), peso de 73kg (dp= 26) e altura de 155cm (dp= 6); e três do sexo masculino com média de idade de 39 anos (dp= 1), peso de 88kg (dp= 5) e altura de 172cm (dp= 4). Pela técnica histoquímica de mATPase, foi realizada análise de proporção das fibras musculares. Após um mês da realização das biópsias, os sujeitos realizaram teste de força isométrica e isocinética concêntrica de flexão e extensão do cotovelo em dinamômetro isocinético. Avaliou-se o pico de torque (PT) isométrico a 90ºs-Õ e 180ºs-Õ e calculou-se o torque relativo 90 (TR90) e 180 (TR180). Para análise estatística, utilizou-se correlação de Spearman (r). RESULTADOS: A proporção de FT2 se correlacionou positivamente com TR180 (r= 0,89, p= 0,01). Uma moderada correlação foi encontrada entre FT2 e TR90 (r= 0,75, p= 0,05). CONCLUSÕES: Os resultados sugerem que o comportamento contrátil das FT2 não foi modificado nestes sujeitos. O dinamômetro isocinético mostrou ser um instrumento que pode avaliar, de forma não invasiva, a predominância do tipo de fibra muscular.
Muscular strength production may be impaired in myopathic patients. Myopathies represent a heterogeneous group of diseases with distinct clinical and morphological characteristics. It has been hypothesized that functional performance findings may be related to the predominant fiber type expressed in the muscle analyzed. OBJECTIVE: To correlate the proportion of type 2 fibers in the biceps brachii muscles of subjects with a clinical hypothesis of myopathy with their peak isometric and isokinetic torque during elbow flexion. METHOD: Seven subjects with a clinical hypothesis of myopathy participated in this study: four females of mean age 37 years (sd = 9), weight 73kg (sd= 26) and height 155cm (sd= 6); and three males of mean age 39 years (sd= 1), weight 88kg (sd= 5) and height 172cm (sd= 4). The muscle fiber proportion was analyzed using the mATPase technique. One month after taking biopsies, the subjects performed concentric isometric and isokinetic strength tests for elbow flexion and extension using an isokinetic dynamometer. The isometric and isokinetic peak torques at 90ºs-Õ and 180ºs-Õ were evaluated and the relative 90º (RT90) and 180º (RT180) torques were calculated. Spearman's correlation (r) was used for statistical analyses. RESULTS: The proportion of type 2 fibers correlated positively with RT180 (r= 0.89, p= 0.01), and there was a moderate correlation with RT90 (r= 0.75, p= 0.05). CONCLUSIONS: The results suggest that the contractile behavior of type 2 fibers was not modified in these subjects. The isokinetic dynamometer was shown to be an instrument capable of noninvasively evaluating muscle fiber type predominance.