RESUMO
Mechanisms of recurrence in oligodendrogliomas are poorly understood. Recurrence might be driven by telomere dysfunction-mediated genomic instability. In a pilot study, we investigated ten patients with oligodendrogliomas at the time of diagnosis (first surgery) and after recurrence (second surgery) using three-dimensional nuclear telomere analysis performed with quantitative software TeloView® (Telo Genomics Corp, Toronto, Ontario, Canada). 1p/19q deletion status of each patient was determined by fluorescent in situ hybridization on touch preparation slides. We found that a very specific 3D telomeric profile was associated with two pathways of recurrence in oligodendrogliomas independent of their 1p/19q status: a first group of 8 patients displayed significantly different 3D telomere profiles between both surgeries (p < 0.0001). Their recurrence happened at a mean of 231.375 ± 117.42 days and a median time to progression (TTP) of 239 days, a period defined as short-term recurrence; and a second group of three patients displayed identical 3D telomere profiles between both surgery samples (p > 0.05). Their recurrence happened at a mean of 960.666 ± 86.19 days and a median TTP of 930 days, a period defined as long-term recurrence. Our results suggest a potential link between nuclear telomere architecture and telomere dysfunction with time to recurrence in oligodendrogliomas, independently of the 1p/19q status.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/diagnóstico , Núcleo Celular/metabolismo , Recidiva Local de Neoplasia , Oligodendroglioma/diagnóstico , Telômero/metabolismo , Adulto , Idoso , Biópsia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 19 , Progressão da Doença , Feminino , Genômica , Humanos , Imageamento Tridimensional , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/genética , Oligodendroglioma/patologia , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Telômero/ultraestrutura , Resultado do TratamentoRESUMO
Os autores apresentam o caso de uma menina de cinco meses de idade com retardo acentuado do desenvolvimento neuromotor, tetraparesia flacida, hiporreflexia e semiptose palpebral bilateral, cuja biopsia muscular demonstrou grande numero de fibras com nucleos centrais, permitindo o diagnostico de miopatia centronuclear (miotubular). Sao analisadas e discutidas a dificuldade de caracterizacao histologica e a variabilidade do quadro clinico deste tipo de miopatia que admite formas de diferente gravidade.