Infantile ZFTA Fusion-Positive Tumor of the Posterior Fossa: Molecular Tumor Board.
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ABSTRACT:
SUBMITTER: Paulson VA
PROVIDER: S-EPMC10309551 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
Publications
Infantile ZFTA Fusion-Positive Tumor of the Posterior Fossa: Molecular Tumor Board.
Paulson Vera A VA Liu Yajuan J YJ Fang He H Browd Sam R SR Hauptman Jason S JS Wright Jason J Lockwood Christina M CM Leary Sarah E S SES Cole Bonnie L BL
JCO precision oncology 20230301
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Project description: Not available
| S-EPMC9837912 | biostudies-literature
Project description:We report a case of spinal ependymoma with ZFTA-YAP1 fusion, occurring in a 5-year-old boy who complained of back pain. It was high-grade ependymoma, developed in the spinal cord at the level of T9-12. Since ZFTA-YAP1 fusion-positive ependymoma has never been reported in the spinal cord, this case is exceptional and worth reporting because the anatomical location, genetics, and epigenetics are important parameters in the classification of the ependymal tumor. This is the first case of spinal ependymoma harboring ZFTA-fusion to be diagnosed by NGS and Sanger studies to the best of our knowledge.
| S-EPMC8713521 | biostudies-literature
Project description:Background and purposePediatric posterior fossa tumors often present with hydrocephalus; postoperatively, up to 25% of patients develop cerebellar mutism syndrome. Arterial spin-labeling is a noninvasive means of quantifying CBF and bolus arrival time. The aim of this study was to investigate how changes in perfusion metrics in children with posterior fossa tumors are modulated by cerebellar mutism syndrome and hydrocephalus requiring pre-resection CSF diversion.Materials and methodsForty-four patients were prospectively scanned at 3 time points (preoperatively, postoperatively, and at 3-month follow-up) with single- and multi-inflow time arterial spin-labeling sequences. Regional analyses of CBF and bolus arrival time were conducted using coregistered anatomic parcellations. ANOVA and multivariable, linear mixed-effects modeling analysis approaches were used. The study was registered at clinicaltrials.gov (NCT03471026).ResultsCBF increased after tumor resection and at follow-up scanning (P = .045). Bolus arrival time decreased after tumor resection and at follow-up scanning (P = .018). Bolus arrival time was prolonged (P = .058) following the midline approach, compared with cerebellar hemispheric surgical approaches to posterior fossa tumors. Multivariable linear mixed-effects modeling showed that regional perfusion changes were more pronounced in the 6 children who presented with symptomatic obstructive hydrocephalus requiring pre-resection CSF diversion, with hydrocephalus lowering the baseline mean CBF by 20.5 (standard error, 6.27) mL/100g/min. Children diagnosed with cerebellar mutism syndrome (8/44, 18.2%) had significantly higher CBF at follow-up imaging than those who were not (P = .040), but no differences in pre- or postoperative perfusion parameters were seen.ConclusionsMulti-inflow time arterial spin-labeling shows promise as a noninvasive tool to evaluate cerebral perfusion in the setting of pediatric obstructive hydrocephalus and demonstrates increased CBF following resolution of cerebellar mutism syndrome.
| S-EPMC9575521 | biostudies-literature
Project description:BackgroundClinicians and machine classifiers reliably diagnose pilocytic astrocytoma (PA) on magnetic resonance imaging (MRI) but less accurately distinguish medulloblastoma (MB) from ependymoma (EP). One strategy is to first rule out the most identifiable diagnosis.ObjectiveTo hypothesize a sequential machine-learning classifier could improve diagnostic performance by mimicking a clinician's strategy of excluding PA before distinguishing MB from EP.MethodsWe extracted 1800 total Image Biomarker Standardization Initiative (IBSI)-based features from T2- and gadolinium-enhanced T1-weighted images in a multinational cohort of 274 MB, 156 PA, and 97 EP. We designed a 2-step sequential classifier - first ruling out PA, and next distinguishing MB from EP. For each step, we selected the best performing model from 6-candidate classifier using a reduced feature set, and measured performance on a holdout test set with the microaveraged F1 score.ResultsOptimal diagnostic performance was achieved using 2 decision steps, each with its own distinct imaging features and classifier method. A 3-way logistic regression classifier first distinguished PA from non-PA, with T2 uniformity and T1 contrast as the most relevant IBSI features (F1 score 0.8809). A 2-way neural net classifier next distinguished MB from EP, with T2 sphericity and T1 flatness as most relevant (F1 score 0.9189). The combined, sequential classifier was with F1 score 0.9179.ConclusionAn MRI-based sequential machine-learning classifiers offer high-performance prediction of pediatric posterior fossa tumors across a large, multinational cohort. Optimization of this model with demographic, clinical, imaging, and molecular predictors could provide significant advantages for family counseling and surgical planning.
| S-EPMC8764569 | biostudies-literature
Project description:Total intracranial volume (TICV) is an essential covariate in brain volumetric analyses. The prevalent brain imaging software packages provide automatic TICV estimates. FreeSurfer and FSL estimate TICV using a scaling factor while SPM12 accumulates probabilities of brain tissues. None of the three provide explicit skull/CSF boundary (SCB) since it is challenging to distinguish these dark structures in a T1-weighted image. However, explicit SCB not only leads to a natural way of obtaining TICV (i.e., counting voxels inside the skull) but also allows sub-definition of TICV, for example, the posterior fossa volume (PFV). In this article, they proposed to use multi-atlas label fusion to obtain TICV and PFV simultaneously. The main contributions are: (1) TICV and PFV are simultaneously obtained with explicit SCB from a single T1-weighted image. (2) TICV and PFV labels are added to the widely used BrainCOLOR atlases. (3) Detailed mathematical derivation of non-local spatial STAPLE (NLSS) label fusion is presented. As the skull is clearly distinguished in CT images, we use a semi-manual procedure to obtain atlases with TICV and PFV labels using 20 subjects who both have a MR and CT scan. The proposed method provides simultaneous TICV and PFV estimation while achieving more accurate TICV estimation compared with FreeSurfer, FSL, SPM12, and the previously proposed STAPLE based approach. The newly developed TICV and PFV labels for the OASIS BrainCOLOR atlases provide acceptable performance, which enables simultaneous TICV and PFV estimation during whole brain segmentation. The NLSS method and the new atlases have been made freely available. Hum Brain Mapp 38:599-616, 2017. © 2016 Wiley Periodicals, Inc.
| S-EPMC5225112 | biostudies-literature
Project description:BackgroundThe risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is known to confer worse prognosis, MRI-based EP risk-profiling is unexplored. We aimed to apply machine learning strategies to link MRI-based biomarkers of high-risk EP and also to distinguish PFA from PFB.MethodsWe extracted 1800 quantitative features from presurgical T2-weighted (T2-MRI) and gadolinium-enhanced T1-weighted (T1-MRI) imaging of 157 EP patients. We implemented nested cross-validation to identify features for risk score calculations and apply a Cox model for survival analysis. We conducted additional feature selection for PFA versus PFB and examined performance across three candidate classifiers.ResultsFor all EP patients with GTR, we identified four T2-MRI-based features and stratified patients into high- and low-risk groups, with 5-year overall survival rates of 62% and 100%, respectively (P < .0001). Among presumed PFA patients with GTR, four T1-MRI and five T2-MRI features predicted divergence of high- and low-risk groups, with 5-year overall survival rates of 62.7% and 96.7%, respectively (P = .002). T1-MRI-based features showed the best performance distinguishing PFA from PFB with an AUC of 0.86.ConclusionsWe present machine learning strategies to identify MRI phenotypes that distinguish PFA from PFB, as well as high- and low-risk PFA. We also describe quantitative image predictors of aggressive EP tumors that might assist risk-profiling after surgery. Future studies could examine translating radiomics as an adjunct to EP risk assessment when considering therapy strategies or trial candidacy.
| S-EPMC9159456 | biostudies-literature
Project description:BackgroundApathy is associated with pervasive and disadvantageous effects on daily functioning. It has been observed transiently in some children after surgery for posterior fossa tumors. In this study, our objective was to examine prevalence, associations, and predictors of apathy in adult survivors of an infantile posterior fossa brain tumor (PFT).MethodsOne hundred seventeen adult survivors of a childhood PFT diagnosed before age 5 years and 60 of their siblings were assessed in a cross-sectional study a mean of 32 years (range, 18-53 years) after survivors' initial tumor diagnoses, using the Marin Apathy Evaluation Scale (AES), the Weschler Abbreviated Scale of Intelligence and the Composite International Diagnostic Interview for psychiatric disorders.ResultsMarin Apathy Evaluation Scale, the Weschler Abbreviated Scale of Intelligence reached or exceeded a criterion score for clinically significant apathy in 35% of survivors, compared with 18% in a sibling comparison group. In both siblings and survivors, apathy was associated with lower verbal and full-scale IQ and, among survivors, with having undergone partial rather than total tumor resection (independent of irradiation status). Apathy was not related to presence of concurrent International Classification of Diseases, 10(th) Revision, depression. Female sex was associated with late apathy after a PFT, with increased likelihood of women reaching the apathy criterion relative to men if they were survivors.ConclusionsClinically significant and potentially treatable apathy occurs relatively commonly in adult survivors of an infantile childhood PFT, particularly women. Clinicians, including those managing posterior fossa pathology in very young children, should be aware of this association, and future research should clarify whether specific treatment-related variables are implicated in increasing this risk of apathy.
| S-EPMC3607262 | biostudies-literature
Project description:Of nine ependymoma molecular groups detected by DNA methylation profiling, the posterior fossa type A (PFA) is most prevalent. We used DNA methylation profiling to look for further molecular heterogeneity among 675 PFA ependymomas. Two major subgroups, PFA-1 and PFA-2, and nine minor subtypes were discovered. Transcriptome profiling suggested a distinct histogenesis for PFA-1 and PFA-2, but their clinical parameters were similar. In contrast, PFA subtypes differed with respect to age at diagnosis, gender ratio, outcome, and frequencies of genetic alterations. One subtype, PFA-1c, was enriched for 1q gain and had a relatively poor outcome, while patients with PFA-2c ependymomas showed an overall survival at 5 years of > 90%. Unlike other ependymomas, PFA-2c tumors express high levels of OTX2, a potential biomarker for this ependymoma subtype with a good prognosis. We also discovered recurrent mutations among PFA ependymomas. H3 K27M mutations were present in 4.2%, occurring only in PFA-1 tumors, and missense mutations in an uncharacterized gene, CXorf67, were found in 9.4% of PFA ependymomas, but not in other groups. We detected high levels of wildtype or mutant CXorf67 expression in all PFA subtypes except PFA-1f, which is enriched for H3 K27M mutations. PFA ependymomas are characterized by lack of H3 K27 trimethylation (H3 K27-me3), and we tested the hypothesis that CXorf67 binds to PRC2 and can modulate levels of H3 K27-me3. Immunoprecipitation/mass spectrometry detected EZH2, SUZ12, and EED, core components of the PRC2 complex, bound to CXorf67 in the Daoy cell line, which shows high levels of CXorf67 and no expression of H3 K27-me3. Enforced reduction of CXorf67 in Daoy cells restored H3 K27-me3 levels, while enforced expression of CXorf67 in HEK293T and neural stem cells reduced H3 K27-me3 levels. Our data suggest that heterogeneity among PFA ependymomas could have clinicopathologic utility and that CXorf67 may have a functional role in these tumors.
| S-EPMC6105278 | biostudies-literature
Project description:Posterior fossa group A ependymomas (EPN_PFA) are characterized by a loss of H3 K27 trimethylation due to either EZHIP overexpression or H3 p.K27M mutation, similar to H3 K27-altered diffuse midline gliomas (DMG), but in reverse proportions. Very little data is available in the literature concerning H3 K27M-mutant EPN_PFA. Here, we retrospectively studied a series of nine pediatric tumors initially diagnosed as H3 K27M-mutant EPN_PFA to compare them to EZHIP-overexpressing EPN_PFA in terms of radiology, follow-up, histopathology, and molecular biology (including DNA-methylation profiling). Seven tumors clustered within EPN_PFA by DNA-methylation analysis and t-distributed stochastic neighbor embedding. Among the two remaining cases, one was reclassified as a DMG and the last was unclassified. H3 K27M-mutant EPN_PFA cases were significantly older than their counterparts with an EZHIP overexpression. Radiological and histopathological central review of our seven H3 K27M-mutant EPN_PFA cases found them to be similar to their counterparts with an EZHIP overexpression. Sequencing analyses revealed HIST1H3B (n = 2), HIST1H3C (n = 2), H3F3A (n = 1), and HIST1H3D (n = 1) K27M mutations (no sequencing analysis available for the last case which was immunopositive for H3K27M). Consequently, HIST1H3C/D mutations are more frequently observed in EPN_PFA than in classic pontine DMG, H3K27-mutant. Overall survival and event-free survival of EZHIP-overexpressing and H3 K27M-mutant EPN_PFA were similar. After surgery and radiation therapy, 5/7 patients were alive at the end of the follow-up. In summary, the diagnosis of EPN_PFA must include tumor location, growth pattern, Olig2 expression, and DNA-methylation profiling before it can be differentiated from DMG, H3 K27-altered.
| S-EPMC9476256 | biostudies-literature
Project description:Genomewide DNA methylation array profiling of nine posterior fossa ependymomas harboring activating mutations in ACVR1. Two samples clustered with the PFA subtype and demonstrated H3K27me3 loss by immunohistochemistry, while the remaining 7 showed retained H3K27me3 and formed a methylation cluster distinct from other ependymal tumors. For these previsouly unpublished cases, the Illumina Infinium EPIC 850k Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissue.
2022-05-01 | GSE196013 | GEO