RESUMO
BACKGROUND: Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations. METHODS: We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant nevus cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation. RESULTS: For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the nevus cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi. CONCLUSIONS: Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal nevus cells. We hypothesise that GNAQ/11 mutant-driven extracellular mitogenic signalling involving YAP activation leads to accumulation of wild-type nevus cells.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Coroide/genética , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Mutação , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Nevo/genética , Fosfoproteínas/metabolismo , Neoplasias da Coroide/metabolismo , Humanos , Imuno-Histoquímica , Nevo/metabolismo , Reação em Cadeia da Polimerase/métodos , Fatores de Transcrição , Proteínas de Sinalização YAPRESUMO
BACKGROUND: Stroke has been a global burden, with increasing morbidity and mortality. Serum cardiac troponin t (cTnT) and creatine kinase (CK-MB) fraction are reported to be elevated in patients admitted with acute ischaemic stroke and high level of these biomarkers indicated more severe stroke and neurologic deficit in some of the patients. OBJECTIVE: To evaluate the serum levels cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) in patients with acute ischaemic stroke and relate the analytes to severity of stroke. METHOD: Patients with clinical diagnosis of ischaemic stroke diagnosed, confirmed by brain Computerized Tomography scan and equal number of apparently healthy age and sex-matched were recruited. Serum cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) were analysed using ELISA method and Stroke severity was determined using National Institute of Health Stroke Score (NIHSS). RESULTS: Mean serum cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) in stroke patients were found to be higher than age sex matched control (p<0.05). NIHS Score of 12.2 ± 5.43 and 9.78 ± 3.97 were observed in Patients with elevated and normal cTnT respectively (p=0.009) while NIHS Score were similar in patients with elevated and normal CK-MB (p = 0.772). CONCLUSION: The mean values of serum cTnT and CK-MB were higher in acute ischaemic stroke patients compared to controls. Serum cardiac Troponin t level may be a significant biomarker of the severity of stroke.