scholarly journals PATH-33. EPIGENOMIC ANALYSIS OF SPINAL EPENDYMOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii171-ii171
Author(s):  
Erika Yamazawa ◽  
Shota Tanaka ◽  
Nagae Genta ◽  
Meguro Hiroko ◽  
Takayoshi Umeda ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dna Methylation ◽  
Profile Analysis ◽  
Neurofibromatosis Type ◽  
Methylation Data ◽  
Who Grade ◽  
Spinal Ependymoma ◽  
Dna Methylation Profile ◽  
Spinal Cord Ependymoma ◽  
The University

Abstract BACKGROUND Ependymomas commonly occur in the fourth ventricle and the spinal cord. Gross total resection, age and WHO grade are known prognostic factors. Ependymomas are currently classified into 9 distinct subgroups by DNA methylation profile analysis. Spinal cord ependymoma is distinct from other subgroups. To investigate heterogeneity within spinal cord ependymoma, we examined DNA methylation profiles. MATERIALS AND METHODS We used Infinium MethylationEPIC array (illumina) to obtain DNA methylation data from frozen specimens of spinal ependymoma resected at the University of Tokyo, Osaka City University, and Tokyo Metropolitan Neurological Hospital. Japan Pediatric Molecular Neuro-Oncology Group provided methylation data for 11 reported cases. Cluster analysis was performed using Cluster3.0. RESULTS We analyzed 34 patients, 21 male and 13 female, aged from 18 to 76 years (median 50.5 years), including 2 cases with neurofibromatosis type 2. WHO grade was grade_3 in 2 cases and grade_2 in others. Clustering of the DNA methylation data showed that WHO grade_3 cases tended to be classified into a subgroup distinct from other cases. CONCLUSION This is the largest DNA methylation profiling study on spinal cord ependymoma to date. The study may suggest a new subgroup correlated with higher WHO grade.

EPCO-01. MOLECULAR PROFILING OF SPINAL CORD EPENDYMOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi1-vi1
Author(s):  
Erika Yamazawa ◽  
Shota Tanaka ◽  
Genta Nagae ◽  
Takayoshi Umeda ◽  
Taijun Hana ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dna Methylation ◽  
Methylation Status ◽  
Neurofibromatosis Type ◽  
Methylation Pattern ◽  
Who Grade ◽  
Spinal Ependymoma ◽  
Fresh Frozen ◽  
Spinal Cord Ependymoma ◽  
The Difference

Abstract BACKGROUND Ependymomas are currently classified into 9 subgroups by DNA methylation profiles. Although spinal cord ependymoma (SP-EPN) is distinct from other tumors, diversity within SP-EPN is still unclear. Here, we used transcriptomic and epigenomic profiles to investigate the diversity among Japanese SP-EPN cases. MATERIALS AND METHODS We analyzed 57 SP-EPN patients (32 males and 25 females, aged from 18 to 78 years, median: 52), including two cases of neurofibromatosis type 2, five cases of grade 3 (WHO grade). We obtained transcriptome (RNA-seq) and DNA methylation (Infinium Methylation EPIC array) data from fresh frozen specimens of SP-EPN resected at the University of Tokyo Hospital and our collaborative groups. RESULTS Three cases had a previous intracranial ependymoma operation. Hierarchical clustering of the DNA methylation data showed that these three cases of intracranial origin as a different cluster from spinal origin. The 45 grade 2 spinal ependymoma showed a relatively homogenous methylation pattern. However, the methylation status of HOX gene cluster regions is compatible with the segment of origin, which reflects the cells of origins are derived after the determination of segment identity. RNA sequencing of 57 cases revealed two subgroups within grade 2. Gene ontology analysis of differentially expressed genes suggested the difference in metabolic state such as rRNA translation and mitochondrial respiration between the two expression subgroups. CONCLUSION Epigenetic analysis indicated the accurate body segment origin of SP-EPN. We observed that metabolic states could divide grade 2 spinal cord ependymoma into 2 subgroups and will present the relationship to clinicopathological information.

scholarly journals Genome‐wide DNA methylation profile analysis in thoracic ossification of the ligamentum flavum

2020 ◽  
Vol 24 (15) ◽  
pp. 8753-8762
Author(s):  
Tianqi Fan ◽  
Xiangyu Meng ◽  
Chuiguo Sun ◽  
Xiaoxi Yang ◽  
Guanghui Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Ligamentum Flavum ◽  
Profile Analysis ◽  
Methylation Profile ◽  
Genome Wide ◽  
Dna Methylation Profile

scholarly journals DNA methylation and transcriptomic alterations define distinct groups in pediatric spinal ependymoma

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv6-iv6
Author(s):  
Omar Ahmad ◽  
Rebecca Chapman ◽  
Lisa Storer ◽  
Li Luo ◽  
Linda Resar ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Oxidative Phosphorylation ◽  
Copy Number ◽  
Transcriptome Profiling ◽  
Tca Cycle ◽  
Methylation Data ◽  
Spinal Ependymoma ◽  
Astrocyte Differentiation ◽  
Dna Copy Number Alterations ◽  
Age Range

Abstract In contrast, compared to adults, spinal ependymomas (SEPN) are less common in childhood and adolescents. Children with these tumours are likely to experience a more aggressive disease course, with a higher rate of local failure, and a higher rate of metastasis. Presently the molecular basis of SEPN is poorly characterized. Therefore, we have analyzed 29 SEPN tumour samples from pediatric patients (female: 11, male: 15; age range: 4 – 21 years) and performed DNA methylation (n=28) and transcriptome profiling (n=29). Unsupervised analysis of methylation data reliably separated these tumours into two distinct groups: one group covering all myxopapillary ependymomas (MPE) and a second group dominated by grade II SPENs (SP-EPN). We identified 242 differentially methylated regions between these two groups, of which 56% showed high methylation levels in MPE, including 22 regions localized on chromosome 6. Genome-wide copy number analysis using methylation data showed differences in numbers and pattern of DNA copy number alterations between these groups. Gain of chromosome 20 (39%) followed by loss of chromosomes 6 (28%), 10 (28%), and 13 (28%) were detected in the MPE group, whereas loss of chromosome 22 was frequent (60%) in the SP-EPN group. Transcriptomic analysis showed that genes associated with oxidative phosphorylation, TCA cycle components, electron transport, and Interferon-gamma production characterize the MPE group whereas potassium ion import and regulation of astrocyte differentiation characterize the SP-EPN group. Taken together, this data suggest that mitochondrial oxidative phosphorylation may drive the regulation of energy metabolism of MPE tumours.

scholarly journals The response of spinal cord ependymomas to bevacizumab in patients with neurofibromatosis Type 2

2017 ◽  
Vol 26 (4) ◽  
pp. 474-482 ◽  
Author(s):  
Katrina A. Morris ◽  
Shazia K. Afridi ◽  
D. Gareth Evans ◽  
Anke E. Hensiek ◽  
Martin G. McCabe ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Response To Treatment ◽  
Spinal Ependymoma ◽  
Bevacizumab Treatment ◽  
Radiological Changes ◽  
And Behavior ◽  
Serial Images

OBJECTIVE People with neurofibromatosis Type 2 (NF2) have a genetic predisposition to nervous system tumors. NF2-associated schwannomas stabilize or decrease in size in over half of the patients while they are receiving bevacizumab. NF2 patients treated with bevacizumab for rapidly growing schwannoma were retrospectively reviewed with regard to ependymoma prevalence and response to treatment. METHODS The records of 95 NF2 patients receiving bevacizumab were retrospectively reviewed with regard to spinal ependymoma prevalence and behavior. The maximum longitudinal extent (MLE) of the ependymoma and associated intratumoral or juxtatumoral cysts were measured on serial images. Neurological changes and patient function were reviewed and correlated with radiological changes. RESULTS Forty-one of 95 patients were found to have ependymomas (median age 26 years; range 11–53 years). Thirty-two patients with a total of 71 ependymomas had scans appropriate for serial assessment with a mean follow-up of 24 months (range 3–57 months). Ependymomas without cystic components showed minimal change in MLE. Twelve patients had ependymomas with cystic components or syringes. In these patients, reductions in MLE were observed, particularly due to decreases in the cystic components of the ependymoma. Clinical improvement was seen in 7 patients, who all had cystic ependymomas. CONCLUSIONS Bevacizumab treatment in NF2 patients with spinal cord ependymomas results in a decrease in the size of intratumoral and juxtatumoral cysts as well as adjacent-cord syringes and a decrease in cord edema. This may provide clinical benefit in some patients, although the changes do not meet the current criteria for radiological tumor response.

Variety of preoperative MRI changes in spinal cord ependymoma of WHO grade II: a case series

2018 ◽  
Vol 28 (2) ◽  
pp. 426-433 ◽  
Author(s):  
Kazuyoshi Kobayashi ◽  
Kei Ando ◽  
Fumihiko Kato ◽  
Koji Sato ◽  
Mitsuhiro Kamiya ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Case Series ◽  
Who Grade ◽  
Grade Ii ◽  
Spinal Cord Ependymoma ◽  
Mri Changes

Ependymoma of the spinal cord in children and adolescents: a retrospective series from the HIT database

2010 ◽  
Vol 6 (2) ◽  
pp. 137-144 ◽  
Author(s):  
Martin Benesch ◽  
Daniela Weber-Mzell ◽  
Nicolas U. Gerber ◽  
Katja von Hoff ◽  
Frank Deinlein ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Overall Survival ◽  
Adjuvant Treatment ◽  
Progression Free Survival ◽  
Gross Total Resection ◽  
Myxopapillary Ependymoma ◽  
Total Resection ◽  
Who Grade ◽  
Free Survival ◽  
Spinal Cord Ependymoma

Object Reports on spinal cord ependymoma in children are rare. The aim of this study was to evaluate the clinical spectrum, treatment, and outcome of children with primary ependymoma of the spinal cord who were registered in the database of the pediatric German brain tumor studies Hirntumor (HIT) '91 and HIT 2000. Methods Between 1991 and 2007, 29 patients (12 male and 17 female, median age at diagnosis 13.6 years) with primary spinal cord ependymoma (myxopapillary ependymoma WHO Grade I, II, and III tumors in 6, 17, and 6 patients, respectively) were identified. Four patients had neurofibromatosis Type 2. Results With a median follow-up of 4.2 years (range 0.48–15 years), 28 patients (96.6%) were alive. Seven patients (24.1%) developed progressive disease or relapse, 2 after gross-total resection (GTR) and 5 after incomplete resection or biopsy. One patient with anaplastic ependymoma (WHO Grade III) died 65 months after diagnosis of disease progression. Primary adjuvant treatment (radiotherapy, chemotherapy, or both) was used in 8 (50%) of 16 patients following GTR and in 9 (82%) of 11 patients who underwent less than a GTR. Three additional patients were treated adjuvantly following progression. Estimated progression-free survival and overall survival rates at 5 years were 72.3% (95% CI 50%–86%) and 100%, respectively. Progression-free survival at 5 years is 84.4% (95% CI 50%–96%) for patients following GTR compared with 57.1% (95% CI 25%–69%) for patients who achieved a less than GTR (p = 0.088, log-rank test). A high relapse incidence (4 of 6) was observed among patients with myxopapillary ependymoma. Conclusions Gross-total resection is the mainstay of treatment for patients with primary spinal cord ependymoma and may be achieved in about 50% of the patients using modern surgical techniques. Primary adjuvant treatment was commonly used in children with spinal cord ependymoma irrespective of the extent of resection or tumor grade. The impact of adjuvant treatment on progression-free and overall survival has to be investigated in a prospective trial.

Prognosis by tumor location in adults with spinal ependymomas

2013 ◽  
Vol 18 (3) ◽  
pp. 226-235 ◽  
Author(s):  
Michael C. Oh ◽  
Joseph M. Kim ◽  
Gurvinder Kaur ◽  
Michael Safaee ◽  
Matthew Z. Sun ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cox Regression ◽  
Statistical Significance ◽  
Cauda Equina ◽  
Tumor Location ◽  
Spinal Cord Tumors ◽  
Prognostic Information ◽  
Who Grade ◽  
Spinal Ependymoma ◽  
Spinal Axis

Object Ependymomas are primary central nervous system tumors that occur more frequently in the spines of adults than they do there in children. Previous studies consist mainly of retrospective single-institutional experiences or case studies. In this study, a comprehensive literature review was performed on reported cases of spinal ependymoma treated with resection to determine whether tumor location along the spinal axis conveys important prognostic information. Methods A PubMed search was performed to identify all papers that included data on patients with spinal ependymoma. Only cases involving adult patients who underwent ependymoma resection with a clearly reported tumor location were included for analysis. Tumor locations were separated into 6 groups: cervicomedullary, cervical, cervicothoracic, thoracic, thoracolumbar, and conus + cauda equina. Kaplan-Meier survival and Cox regression analyses were performed to determine the effect of tumor location on progression-free survival (PFS) and overall survival (OS). Results A total of 447 patients who underwent resection of spinal ependymomas with clearly indicated location of tumor were identified. The most common locations of spinal ependymomas were the cervical (32.0%) and conus + cauda equina (26.8%) regions. The thoracolumbar and cervicomedullary regions had the fewest tumors (accounting for, respectively, 5.1% and 3.4% of the total number of cases). The conus + cauda equina and thoracolumbar regions had the highest percentage of WHO Grade I tumors, while tumors located above these regions consisted of mostly WHO Grade II tumors. Despite the tendency for benign grades in the lower spinal regions, PFS for patients with spinal ependymomas in the lower 3 regions (thoracic, thoracolumbar, conus + cauda equina) was significantly shorter (p < 0.001) than for those with tumors in the upper regions (cervicomedullary, cervical, cervicothoracic), but the difference in OS did not achieve statistical significance (p = 0.131). Conclusions Spinal ependymomas along different regions of spinal axis have different characteristics and clinical behaviors. Tumor grade, extent of resection, and PFS varied by tumor location (upper vs lower spinal regions), while OS did not. Recurrence rates were higher for the lower spinal cord tumors, despite a greater prevalence of lower WHO grade lesions, compared with upper spinal cord tumors, suggesting that tumor location along the spinal axis is an important prognostic factor.

Multisegmental Versus Monosegmental Intramedullary Spinal Cord Ependymomas: Perioperative Neurological Functions and Surgical Outcomes

2021 ◽  
Author(s):  
Chenlong Yang ◽  
Jianjun Sun ◽  
Jingcheng Xie ◽  
Bin Liu ◽  
Tao Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Surgical Outcomes ◽  
Functional Outcomes ◽  
Japanese Orthopaedic Association ◽  
Who Grade ◽  
Intramedullary Spinal Cord ◽  
Clinical Prognosis ◽  
Spinal Cord Ependymoma

Abstract Objectives: Multiple factors, such as tumor size, lateralization, tumor location, accompanying syringomyelia, and regional spinal cord atrophy, may affect the resectability and clinical prognosis of intramedullary spinal cord ependymomas. However, whether long-segmental involvement of the spinal cord may impair functional outcomes remains unclear. This study was aimed to compare perioperative neurological functions and long-term surgical outcomes between multisegmental ependymomas and their monosegmental counterparts.Methods: A total of 54 patients with intramedullary spinal cord ependymoma (WHO Grade II) were enrolled, and all of them underwent surgical resection. The patients were classified into the multisegmental group (n=40) and the monosegmental group (n=14). Perioperative and long-term (average follow-up period, 53.5 ± 18.2 months) neurological functions were evaluated using the modified McCormick (mMC) scale and the modified Japanese Orthopaedic Association (mJOA) scoring system.Results: Preoperative neurological functions in the multisegmental group were significantly worse than those in the monosegmental group (P < 0.05). However, postoperative short-term neurological functions, as well as long-term functional outcomes, were similar between the two groups (P > 0.05). Logistic regression analysis showed that only preoperative mMC and mJOA scores were significantly correlated with neurological improvement during the follow-up period (P < 0.05).Conclusion: Multisegmental involvement of the spinal cord is associated with worse neurological functions in patients with intramedullary spinal cord ependymoma, while the long-term prognosis is not affected. The preoperative neurological status of the patient is the only predictor of long-term functional improvement.

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