Allelic loss (or loss of heterozygosity) of chromosome 1p is a statistically significant predictor of chemosensitivity, and combined loss involving chromosomes 1p and 19q is statistically significantly associated with both chemosensitivity and longer recurrence-free survival after chemotherapy. Moreover, in both univariate and multivariate analyses, losses involving both chromosomes 1p and 19q were strongly associated with longer overall survival, whereas CDKN2A gene deletions and ring enhancement (i.e., contrast enhancement forming a rim around the tumor) on neuroimaging were associated with a significantly worse prognosis. The inverse relationship between CDKN2A gene deletions and losses of chromosomes 1p and 19q further implies that these differential clinical behaviors reflect two independent genetic subtypes of anaplastic oligodendroglioma. These results suggest that molecular genetic analysis may aid therapeutic decisions and predict outcome in patients with anaplastic oligodendrogliomas.
The prognostic impact of TERT mutations has been controversial in IDH-wild tumors, particularly in glioblastomas (GBM). The controversy may be attributable to presence of potential confounding factors such as MGMT methylation status or patients’ treatment. This study aimed to evaluate the impact of TERT status on patient outcome in association with various factors in a large series of adult diffuse gliomas. We analyzed a total of 951 adult diffuse gliomas from two cohorts (Cohort 1, n = 758; Cohort 2, n = 193) for IDH1/2, 1p/19q, and TERT promoter status. The combined IDH/TERT classification divided Cohort 1 into four molecular groups with distinct outcomes. The overall survival (OS) was the shortest in IDH wild-type/TERT mutated groups, which mostly consisted of GBMs (P < 0.0001). To investigate the association between TERT mutations and MGMT methylation on survival of patients with GBM, samples from a combined cohort of 453 IDH-wild-type GBM cases treated with radiation and temozolomide were analyzed. A multivariate Cox regression model revealed that the interaction between TERT and MGMT was significant for OS (P = 0.0064). Compared with TERT mutant-MGMT unmethylated GBMs, the hazard ratio (HR) for OS incorporating the interaction was the lowest in the TERT mutant-MGMT methylated GBM (HR, 0.266), followed by the TERT wild-type-MGMT methylated (HR, 0.317) and the TERT wild-type-MGMT unmethylated GBMs (HR, 0.542). Thus, patients with TERT mutant-MGMT unmethylated GBM have the poorest prognosis. Our findings suggest that a combination of IDH, TERT, and MGMT refines the classification of grade II-IV diffuse gliomas.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0351-2) contains supplementary material, which is available to authorized users.
Background and Purpose-With many patients living long after microsurgical aneurysm clipping for subarachnoid hemorrhage (SAH) and with the evolution of intravascular procedures as less invasive alternatives, knowledge of the long-term results of clipping is becoming important. Methods-Of 412 patients who underwent clipping of ruptured or unruptured cerebral aneurysms at our institution between 1976 and 1994 and who survived Ͼ3 years after surgery, 225 patients who were in good general condition and younger than 80 years were offered follow-up angiography to detect newly formed aneurysms. Of the 225, 80 patients (35.6%) agreed to undergo angiography. In addition, 32 patients underwent angiography for new medical indications other than SAH. Therefore, 112 patients underwent angiography, representing a total of 140 clipped aneurysms. Results-The mean interval from surgery was 9.3 years for all patients and 9.0 years for the clipped aneurysms (range 3 to 21 years). Four aneurysm regrowths were detected of the 140 (2.9%) clipped aneurysms, representing 3 of 125 completely clipped aneurysms, 1 of 14 incompletely clipped aneurysms, and 0 of 1 aneurysm not studied with postoperative angiography. De novo aneurysms were detected in 9 of 112 (8.0%) patients. The annual rate of de novo aneurysm formation was 0.89%. Conclusions-This study shows that the annual rate of de novo aneurysm formation is relatively high (0.89%) and that the cumulative risk becomes significant after 9 years. In consideration of the fatality rate of SAH, follow-up angiography may be indicated for patients with clipped aneurysms 9 to 10 years after surgery.
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