- To treat or not to treat? A retrospective multicenter assessment of survival in patients with IDH-mutant low-grade glioma based on adjuvant treatment. [Journal Article]
- JNJ Neurosurg 2019 Jul 19; :1-8
- CONCLUSIONS: In this series of IDH-mutated LGGs, adjuvant treatment with RT, CT with temozolomide (TMZ), or the combination of both showed no significant advantage in terms of PFS and OS. Even in high-risk patients, the authors observed a similar significantly negative impact of adjuvant treatment on PFS and OS. These results underscore the importance of a CTR in LGG. Whether patients ≥ 40 years old should receive adjuvant treatment despite a CTR should be a matter of debate. A potential tumor dedifferentiation by administration of early TMZ, RT, or RT+CT in IDH-mutated LGG should be considered. However, these data are limited by the retrospective study design and the potentially heterogeneous indication for adjuvant treatment.
- The crystal structure of Capicua HMG-box domain complexed with the ETV5-DNA and its implications for Capicua-mediated cancers. [Journal Article]
- FJFEBS J 2019 Jul 19
- Capicua (CIC) is a transcriptional repressor and functions downstream of the receptor tyrosine kinase (RTK) signaling pathway. Somatic mutations found in the HMG-box DNA binding domain in CIC have be…
Capicua (CIC) is a transcriptional repressor and functions downstream of the receptor tyrosine kinase (RTK) signaling pathway. Somatic mutations found in the HMG-box DNA binding domain in CIC have been implicated in several cancers such as oligodendroglioma, oligoastrocytoma, and adenocarcinoma. However, the molecular basis of the DNA binding of CIC and the effect of the somatic mutations found in cancers on DNA binding have not been investigated. Here, we report the crystal structure of the HMG-box domain of CIC complexed with its target DNA, the promoter of Ets Translocation Variant 5 (ETV5). The structure shows that the HMG-box domain has an L-shaped structure and recognizes the minor groove leading to DNA bending. Our structure combined with an electrophoretic mobility shift assay (EMSA) revealed that cancer-associated mutations in the HMG-box domain abrogate the interaction with DNA. These results provide the molecular insight into the DNA binding of CIC and reveal the effects of carcinogenic mutations on DNA binding. This article is protected by copyright. All rights reserved.
- Real-time augmented reality for delineation of surgical margins during neurosurgery using autofluorescence lifetime contrast. [Journal Article]
- JBJ Biophotonics 2019 Jul 15; :e201900108
- Current clinical brain imaging techniques used for surgical planning of tumor resection lack intraoperative and real-time feedback; hence surgeons ultimately rely on subjective evaluation to identify…
Current clinical brain imaging techniques used for surgical planning of tumor resection lack intraoperative and real-time feedback; hence surgeons ultimately rely on subjective evaluation to identify tumor areas and margins. We report a fluorescence lifetime imaging (FLIm) instrument (excitation: 355 nm; emission spectral bands: 390/40 nm, 470/28 nm, 542/50 nm, and 629/53 nm) that integrates with surgical microscopes to provide real-time intraoperative augmentation of the surgical field of view with fluorescent derived parameters encoding diagnostic information. We show the functionality and safety features of this instrument during neurosurgical procedures in patients undergoing craniotomy for the resection of brain tumors and/or tissue with radiation damage. We demonstrate in three case studies the ability of this instrument to resolve distinct tissue types and pathology including cortex, white matter, tumor, and radiation-induced necrosis. In particular, two patients with effects of radiation induced necrosis exhibited longer fluorescence lifetimes and increased optical redox ratio on the necrotic tissue with respect to non-affected cortex, and an oligodendroglioma resected from a third patient reported shorter fluorescence lifetime and a decrease in optical redox ratio than the surrounding white matter. These results encourage the use of FLIm as a label-free and non-invasive intraoperative tool for neurosurgical guidance. This article is protected by copyright. All rights reserved.
- [IDH、TERT and 1p/19q predicting clinical outcomes in patients with anaplastic oligodendroglioma]. [Journal Article]
- ZYZhonghua Yi Xue Za Zhi 2019 Jul 02; 99(25):1959-1962
- CONCLUSIONS: IDH-mtand (or) 1p/19q codeletedpredicted better survivals in patients with anaplastic oligodendroglioma. IDH and 1p/19q deleted might be a biomarker for predicting prognosis of patients with anaplastic oligodendroglioma.
- Canine Ependymoma: Diagnostic Criteria and Common Pitfalls. [Journal Article]
- VPVet Pathol 2019 Jul 02; :300985819859872
- Reports of canine ependymoma are generally restricted to single case reports with tumor incidence estimated at 2% to 3% of primary central nervous system (CNS) tumors. While most commonly reported in…
Reports of canine ependymoma are generally restricted to single case reports with tumor incidence estimated at 2% to 3% of primary central nervous system (CNS) tumors. While most commonly reported in the lateral ventricle, tumors can occur anywhere in the ventricular system and in extraventricular locations. Rosettes and pseudorosettes are a common histologic feature; however, these features can be mimicked by other CNS neoplasms. Thirty-seven potential ependymoma cases were identified in a retrospective database search of 8 institutions, and a histologic review of all cases was conducted. Of 37 cases, 22 candidate cases were further subjected to a consensus histologic and immunohistochemical review, and only 5 of 37 (13.5%) were conclusively identified as ependymoma. The neuroanatomic locations were the lateral ventricle (3/5), third ventricle (1/5), and mesencephalic aqueduct (1/5). Subtypes were papillary (4/5) and tanycytic (1/5). Histologic features included rosettes (5/5), pseudorosettes (5/5), ependymal canals (2/5), tanycytic differentiation (1/5), blepharoplasts (1/5), ciliated cells (1/5), and high nuclear to cytoplasmic ratio (5/5). Immunolabeling for GFAP (4/4) and CKAE1/3 (3/4) was found in pseudorosettes, rosettes, and scattered individual neoplastic cells. Diffuse but variably intense cytoplasmic S100 immunolabeling was detected in 3 of 4 cases. Olig2 intranuclear immunolabeling was observed in less than 1% of the neoplastic cells (3/3). Tumors that had pseudorosettes and mimicked ependymoma included oligodendroglioma, choroid plexus tumor, pituitary corticotroph adenoma, papillary meningioma, and suprasellar germ cell tumor. These findings indicate that canine ependymoma is an extremely rare neoplasm with histomorphologic features that overlap with other primary CNS neoplasms.
- Synchronous identification of a dysembryoplastic neuroepithelial tumor (DNET) and an oligodendroglioma in a patient: A case report. [Journal Article]
- CNClin Neuropathol 2019 Jul 02
- Synchronous gliomas of different histopathology are quite rare in non-syndromic, non-irradiated patients. Although "mixed" gliomas are not infrequent, and malignant gliomas often contain areas of dis…
Synchronous gliomas of different histopathology are quite rare in non-syndromic, non-irradiated patients. Although "mixed" gliomas are not infrequent, and malignant gliomas often contain areas of disparate differentiation (e.g., glioblastoma with ependymal differentiation), it is unusual to find gliomas of different lineage presenting concurrently. We present a case of synchronous gliomas, one dysembryoplastic neuroepithelial tumor (DNET) and the other oligodendroglioma. .
- Anaplastic Oligodendroglioma with Transdural Extension. [Journal Article]
- WNWorld Neurosurg 2019 Jun 26
- Oligodendrogliomas, the third most common primary gliomas, have a strict molecular definition, characterized by the combined presence of IDH mutation and 1p19q codeletion. Here in, we describe an ext…
Oligodendrogliomas, the third most common primary gliomas, have a strict molecular definition, characterized by the combined presence of IDH mutation and 1p19q codeletion. Here in, we describe an extremely unusual case of molecularly-defined anaplastic oligodendroglioma with transdural extension into the frontal and ethmoid sinuses, without prior neurosurgical intervention or radiotherapy. The molecular profile of the tumour will also be provided. To the best of our knowledge, this has never been reported before. Most of the previously reported glial tumours with transdural extension were cases of histologically proven glioblastoma and gliosarcomas, typically seen in the context of prior neurosurgical intervention and/or radiotherapy. This case adds to the limited literature on oligodendrogliomas with transdural extension. Further studies are needed to elucidate the relationship between the incidence of transdural extension and the molecular subtypes of oligodendrogliomas.
- Bone metastases from a 1p/19q codeleted and IDH1-mutant anaplastic oligodendroglioma: a case report. [Journal Article]
- JMJ Med Case Rep 2019 Jun 28; 13(1):202
- CONCLUSIONS: This case joins less than 20 other reported cases of oligodendroglioma bone marrow metastasis, and is one of only a handful of cases of diffuse bone metastases beyond the axial skeleton. To the best of our knowledge, the early relapse of 1p/19q codeleted anaplastic oligodendroglioma with this distribution of metastases has never been described in the literature.
- Deep sequencing of a recurrent oligodendroglioma and the derived xenografts reveals new insights into the evolution of human oligodendroglioma and candidate driver genes. [Journal Article]
- OOncotarget 2019 Jun 04; 10(38):3641-3653
- We previously reported the establishment of a rare xenograft derived from a recurrent oligodendroglioma with 1p/19q codeletion. Here, we analyzed in detail the exome sequencing datasets from the recu…
We previously reported the establishment of a rare xenograft derived from a recurrent oligodendroglioma with 1p/19q codeletion. Here, we analyzed in detail the exome sequencing datasets from the recurrent oligodendroglioma (WHO grade III, recurrent O2010) and the first-generation xenograft (xenograft1). Somatic SNVs and small InDels (n = 80) with potential effects at the protein level in recurrent O2010 included variants in IDH1 (NM_005896:c.395G>A; p. Arg132His), FUBP1 (NM_003902:c.1307_1310delTAGA; p.Ile436fs), and CIC (NM_015125:c.4421T>G; p.Val1474Gly). All but 2 of these 80 variants were also present in xenograft1, along with 7 new variants. Deep sequencing of the 87 SNVs and InDels in the original tumor (WHO grade III, primary O2005) and in a second-generation xenograft (xenograft2) revealed that only 11 variants, including IDH1 (NM_005896:c.395G>A; p. Arg132His), PSKH1 (NM_006742.2:c.650G>A; p.Arg217Gln), and SNX12 (NM_001256188:c.470G>A; p.Arg157His), along with a variant in the TERT promoter (C250T, NM_198253.2: c.-146G>A), were already present in primary O2005. Allele frequencies of the 11 variants were calculated to assess their potential as putative driver genes. A missense change in NDST4 (NM_022569:c.2392C>G; p.Leu798Val) on 4q exhibited an increasing allele frequency (~ 20%, primary O2005, 80%, recurrent O2010 and 100%, xenograft1), consistent with a selection event. Sequencing of NDST4 in a cohort of 15 oligodendrogliomas, however, revealed no additional cases with potential protein disrupting variants. Our analysis illuminated a tumor evolutionary series of events, which included 1p/19q codeletion, IDH1 R132H, and TERT C250T as early events, followed by loss of function of NDST4 and mutations in FUBP1 and CIC as late events.
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- Defining an Intermediate-risk Group for Low-grade Glioma: A National Cancer Database Analysis. [Journal Article]
- ARAnticancer Res 2019; 39(6):2911-2918
- CONCLUSIONS: Due to inferior OS for patients with LR-LGG with >5 cm, non-oligodendroglioma tumors, we propose an 'intermediate-risk' clinical classification for this subset.