Distinct TERT promoter C228T and C250T mutations in a patient with an oligodendroglioma: A case report.

The majority of oligodendroglial tumors harbor mutations in the telomerase reverse transcriptase (TERT) gene (TERT) promoter and the isocitrate dehydrogenase 1/2 (IDH1/2) gene (IDH1/2), as well as 1p/19q codeletion. Generally, TERT promoter mutations, C250T and C228T, are mutually exclusive. We present a case of oligodendroglioma harboring both C250T and C228T mutations in TERT promoter. A 38-year-old man presented with grand mal seizures and underwent a resection surgery for a left frontal lobe tumor. He was pathologically diagnosed as having oligodendroglioma and was carefully observed. At 48 years of age, he underwent another resection surgery due to tumor regrowth, with the pathological diagnosis of anaplastic oligodendroglioma. Genetic analysis of the initial tumor specimen revealed IDH1 R132H mutation and both C250T and C228T mutations in TERT promoter. Using mutation-specific primers, two mutations were considered to be distributed in different alleles. In the tumor specimen obtained during the second surgery, IDH1 R132H mutation was detected to be similar to that of the initial specimen; however, only C228T mutation was detected in TERT promoter. The 1p/19q codeletion was detected in both the initial and recurrent tumor specimens. According to the sequencing data from the two tumor specimens, although TERT promoter mutation has been considered to be an early genetic event in the tumorigenesis of oligodendroglial tumors, it is likely that the C250T and C228T mutations in TERT promoter are subclonally distributed in the same tumor specimen of the present case.

Classification of Diffuse Glioma Subtype from Clinical-Grade Pathological Images Using Deep Transfer Learning.

Diffuse gliomas are the most common primary brain tumors and they vary considerably in their morphology, location, genetic alterations, and response to therapy. In 2016, the World Health Organization (WHO) provided new guidelines for making an integrated diagnosis that incorporates both morphologic and molecular features to diffuse gliomas. In this study, we demonstrate how deep learning approaches can be used for an automatic classification of glioma subtypes and grading using whole-slide images that were obtained from routine clinical practice. A deep transfer learning method using the ResNet50V2 model was trained to classify subtypes and grades of diffuse gliomas according to the WHO's new 2016 classification. The balanced accuracy of the diffuse glioma subtype classification model with majority voting was 0.8727. These results highlight an emerging role of deep learning in the future practice of pathologic diagnosis.

IDH1 mutation is prognostic for diffuse astrocytoma but not low-grade oligodendrogliomas in patients not treated with early radiotherapy.

Despite accumulating knowledge regarding molecular backgrounds, the optimal management strategy for low-grade gliomas remains controversial. One reason is the marked heterogeneity in the clinical course. To establish an accurate subclassification of low-grade gliomas, we retrospectively evaluated isocitrate dehydrogenase-1 (IDH1) mutation in clinical specimens of diffuse astrocytomas (DA) and oligodendroglial tumors separately. No patients were treated with early radiotherapy, and modified PCV chemotherapy was used for postoperative residual tumors or recurrence in oligodendroglial tumors. Immunohistochemical evaluation of IDH status, p53 status, O(6)-methylguanine methyltransferase expression, and the MIB-1 index were performed. The 1p and 19q status was analyzed with fluorescence in situ hybridization. Ninety-four patients were followed for a median period of 8.5 years. For DAs, p53 was prognostic for progression- free survival (PFS) and IDH1 was significant for overall survival (OS) with multivariate analysis. In contrast, for oligodendroglial tumors, none of the parameters was significant for PFS or OS. Thus, the significance of IDH1 mutation is not clear in oligodendroglial tumors that are homogeneously indolent and chemosensitive. In contrast, DAs are heterogeneous tumors including some potentially malignant tumors that can be predicted by examining the IDH1 mutation status.

PC or PCV, That Is the Question: Primary Anaplastic Oligodendroglial Tumors Treated with Procarbazine and CCNU With and Without Vincristine.

BACKGROUND: While procarbazine with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (PC) added to vincristine (PCV) was proven beneficial in the treatment of co-deleted anaplastic oligodendroglioma (AO), the question of whether PC alone is sufficient is important, as vincristine adds toxicity with uncertain benefit. This retrospective study provides a comparison of PC and PCV. PATIENTS AND METHODS: Patients diagnosed with AO treated at the M.D. Anderson Cancer Center from June 1, 1993 to October 13, 2009 were selected from the database and were eligible if diagnosed with a primary AO and treated with either PC or PCV at some point. Ninety-seven patients were treated with such chemotherapy before first progression. RESULTS: Initial treatment included radiation and chemotherapy (81.4%) or chemotherapy alone (18.6%). Twenty-one patients (21.6%) received PC during primary treatment, while 76 patients (78.4%) received PCV. Eleven patients reported neurotoxicity in the PCV arm vs. none in the PC arm. Out of the 97 patients, 45 were alive at last contact, with a median follow-up of 9.9 years. The median overall survival was 6.5 years (95% confidence interval=4.8-16.7 years), while the median progression-free survival was 2.9 years (95% confidence interval=2.0-6.3 years); these differences were not significant (p=0.61 and p=0.28, respectively). CONCLUSION: Initial therapy with PC achieved comparable results to those of PCV with a median follow-up of 9.9 years. Neurotoxicity was more frequent with vincristine. Although selecting only for patients with AO, rather than those with mixed histology, increased the likelihood of selecting for patients with tumors with co-deletions, further studies with correlative co-deletion status are required.