Tert Promoter Mutations Occur In Gliomas And Are Biomarkers Of Poor Outcome In The Chinese Population

TERT promoter mutations occur in gliomas and are biomarkers of poor outcome in the Chinese populationObjective Recent findings have established frequent mutations in the promoter region of telomerase reverse transcriptase in a multitude of cancers, including thyroid carcinoma, live cancer, bladder cancer, and melanoma. And, the TERT promoter mutations were associated with a poor prognosis among all gliomas patients. However, the distribution of the TERT promoter mutations in Chinese populations has not been reported to data. In this study, we investigated the distribution of TERT promoter mutations in Chinese populations and also assessed the association of those mutations with patient overall survival.Methods In the present study, we screened for TERT promoter mutations by direct DNA sequencing in a population-based collection of 78 gliomas and 19 normal brain tissues. The Fisher’s exact probability test was used to assess the association of clinicalparameters with the TERT promoter mutations. The Kaplan-Meier method and the log-rank test were used for univariate survival analysis. Multivariate Cox regression models were applied to assess the impact of TERT promoter mutations on glioma patients’ survival.Results We identified TERT promoter mutations in 25(32.1%) gliomas, including 0% in grade I tumors, 33.3% in grade II tumors, 30.0% in grade III tumors and 36.4 in grade IV tumors. TERT promoter mutations were also common in oligoastrocytomas and glioblastomas, however, TERT promoter mutations were less frequently identified in Grade II-III astrocytomas and oligodendrogliomas. Furthermore, the TERT promoter mutations has not been identified in normal brain tissues. Among the 78 gliomas, the median overall survival of those tumors harboring mutations in TERT promoter was longer than those tumors without the TERT promoter mutations(P=0.001). Tumors with mutations in the TERT promoter, which was the predominant signature present in low grade gliomas had the poorest overall survival(P=0.019), even in high grade gliomas(P=0.018). Multivariate analysis revealed TERT promoter mutations and without postoperative adjuvant therapy as significant prognostic factors for shorter survival(P=0.002,HR=3.486,95%CI:1.591~7.637; P=0.004,HR=0.331,95%CI:0.156~0.699).Conclusion TERT promoter mutations highly frequent occurred in gliomas, and very rare in normal somatic cells. The discovery of TERT promoter mutations in subsets of gliomas creates an opportunity for genomics to supplement histopathological analysis. The association of the mutations with patient overall survival can be a unique putative molecular marker with individualized prognostic potential.The clinical features and strategies in the treatment of gliomas in the elderlyObjective Gliomas are the most common primary malignant brain tumor in adults. It is an aggressive primary brain tumor and associated with a poor prognosis. With the increasing aging population and advances in imaging diagnosis, the age-adjusted incidence of gliomas has increased over recent years. Clinical management of elderly patients with gliomas is different to younger population, owing to multiple comorbidities, polypharmacy, decreased tolerance to chemotherapy, and an increased risk of radiation-induced neurotoxicity. Until now, the clinical features and optimal treatment of elderly patients with gliomas has not been reported in China. Therefore, it is very important to fully recognize the characteristics of elderly patients with gliomas, which may improve the diagnosis and treatment level.Methods Between May 2011 and August 2014, the clinical features and outcomes of 24 patients over 60 years old with gliomas were retrospectively reviewed at our institute.Results The average patient age was 64.7 years. 17 patients had comorbidities besidesgliomas in this study and 10 patients had more than two comorbidities. All the patients were treated by microsurgery. Total removal of tumor was achieved in 9 patients, subtotal removal in 6 and near total removal in 9. Thirteen patients harbored glioblastomas, 4 patients anaplastic astrocytoma, 2 patients anaplastic oligoastrocytomas, 1 patient anaplastic ependymoma, 1 patient astrocytomas, 1 patient oligodendrogliomas, 1 patient gliomatosis cerebri, and an additional patient suffered from glioma with unclear classification. The most common complications were neurological dysfunctions, intracranial and pulmonary infections. 20 patients were followed up from 2.4 to 38.5 months; however, 1 patient was lost to follow up, 3 patients died of postoperative complications. The 1- and 2-year survival rates were 54.9% and 36.6%. The overall survival time was 29.8±5.02 months for the patients treated with concurrent chemotherapy and radiotherapy, followed by 6.6±1.3 months for the patients treated with chemotherapy. For patients who only received surgery, the overall survival time was 6.2±2.4 months.Conclusion Glioma in elderly is easily misdiagnosed. It is critical to strengthen management concentrated on comorbidities during perioperative period. Concurrent TMZ chemotherapy and radiotherapy after maximum safe surgical resection of the tumors can improve the overall survival time of glioma patients in the elderly.