RESUMO
NSD3 (nuclear receptor-binding SET domain protein 3) is a member of the NSD histone methyltransferase family of proteins. In recent years, it has been identified as a potential oncogene in certain types of cancer. The NSD3 gene encodes three isoforms, the long version (NSD3L), a short version (NSD3S) and the WHISTLE isoforms. Importantly, the NSD3S isoform corresponds to the N-terminal region of the full-length protein, lacking the methyltransferase domain. The chromosomal location of NSD3 is frequently amplified across cancer types, such as breast, lung, and colon, among others. Recently, this amplification has been correlated to a chromothripsis event, that could explain the different NSD3 alterations found in cancer. The fusion proteins containing NSD3 have also been reported in leukemia (NSD3-NUP98), and in NUT (nuclear protein of the testis) midline carcinoma (NSD3-NUT). Its role as an oncogene has been described by modulating different cancer pathways through its methyltransferase activity, or the short isoform of the protein, through protein interactions. Specifically, in this review we will focus on the functions that have been characterized as methyltransferase dependent, and those that have been correlated with the expression of the NSD3S isoform. There is evidence that both the NSD3L and NSD3S isoforms are relevant for cancer progression, establishing NSD3 as a therapeutic target. However, further functional studies are needed to differentiate NSD3 oncogenic activity as dependent or independent of the catalytic domain of the protein, as well as the contribution of each isoform and its clinical significance in cancer progression.
Assuntos
Histona-Lisina N-Metiltransferase , Neoplasias , Proteínas Nucleares , Humanos , Masculino , Carcinoma/enzimologia , Leucemia/enzimologia , Oncogenes , Isoformas de Proteínas/genética , Histona-Lisina N-Metiltransferase/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias/enzimologia , Neoplasias/patologiaRESUMO
Introducción. El tratamiento quirúrgico de las lesiones por proyectil de arma de fuego en la columna es controversial; sin embargo, el déficit neurológico es uno de los criterios para su indicación. Presentación del caso. Hombre de 21 años que ingresó al servicio de urgencias de un hospital de tercer nivel en Bogotá, Colombia, por múltiples heridas de arma de fuego, paraplejía, hipoestesia en miembros inferiores y silla de montar, e incapacidad para moverse, por lo que se realizó toracotomía y laparotomía. Ante la ausencia de fuerza muscular y reflejos, se diagnosticó lesión de la médula espinal de grado A según la American Spinal Injury Association Impairment Scale (ASIA). A las 12 horas del ingreso, se llevó al paciente a extracción quirúrgica de un proyectil (laminectomía y durotomía longitudinal) sin lograr la extracción, por lo que se utilizó fluoroscopia, en la que se observó que la bala había migrado cefálicamente al espacio intervertebral L4-L5. Se realizó laminectomía de L4-L5, exposición del saco dural y durotomía longitudinal, logrando la extracción del proyectil. A los 20 días se observó mejoría de la función motora y la fuerza muscular, contracción voluntaria de cuádriceps y grado C en ASIA.Conclusión. La extracción del proyectil en lesiones de la médula espinal se recomienda cuando hay migración de este en el canal medular. Se sugiere usar fluoroscopia antes y después de la cirugía
Introduction: Surgical treatment of spinal gunshot wounds is controversial, however, neurological deficit is one of the criteria for its indication. Case presentation: A 21-year-old man was admitted to the emergency department of a tertiary care hospital in Bogotá, Colombia, due to multiple gunshot wounds, paraplegia, hypoesthesia in the lower limbs and saddle area, and inability to move, for which thoracotomy and laparotomy were performed. Given the absence of muscle strength and reflexes, a grade A spinal cord injury was diagnosed according to the American Spinal Injury Association Impairment Scale (ASIA). Twelve hours after admission, the patient was taken to surgery for the removal of a firearm projectile (laminectomy and longitudinal durotomy) without achieving the extraction, so a fluoroscopy was carried out, in which it was observed that the bullet had migrated cephalad to the L4-L5 intervertebral space. L4-L5 laminectomy, dural sac exposure, and longitudinal durotomy were performed, leading to the removal of the projectile. After 20 days, improvement of motor function and muscle strength, voluntary contraction of quadriceps, and grade C in ASIA were reported.Conclusion: Projectile removal in spinal cord injuries is recommended when the projectile migrates into the spinal canal. Fluoroscopy is recommended before and after surgery