Adult intracranial ependymoma - relevance of DNA methylation profiling for diagnosis, prognosis and treatment
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PROVIDER: PRJNA930690 | ENA |
REPOSITORIES: ENA
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Project description:Background: A methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain unclear. Here, we retrospectively evaluate the impact of surgery and radiotherapy on outcome after molecular reclassification of adult intracranial ependymomas. Methods: Tumors diagnosed as intracranial ependymomas from 170 adult patients collected from eight diagnostic institutions were subjected to DNA methylation profiling. Molecular classes, patient characteristics, and treatment were retrospectively correlated with progression-free survival (PFS). Results: The classifier indicated an ependymal tumor in 73.5%, a different tumor entity in 10.6% and non-classifiable tumors in 15.9% of cases, respectively. The most prevalent molecular classes were posterior fossa ependymoma group B (EPN-PFB, 32.9%), posterior fossa subependymoma (PF-SE, 25.9%), and supratentorial ZFTA fusion-positive ependymoma (EPN-ZFTA, 11.2%). With a median follow-up of 60.0 months, the 5- and 10-year-PFS rates were 64.5% and 41.8% for EPN-PFB, 67.4% and 45.2% for PF-SE and 60.3% and 60.3% for EPN-ZFTA. In EPN-PFB, but not in other molecular classes, gross total resection (p=0.009) and postoperative radiotherapy (p=0.007) were significantly associated with improved PFS in multivariable analysis. Histological tumor grading (WHO 2 vs. 3) was not a predictor of prognosis within molecularly defined ependymoma classes. Conclusions: DNA methylation profiling improves diagnostic accuracy and risk stratification in adult intracranial ependymoma. The molecular class of PF-SE is unexpectedly prevalent among adult tumors with ependymoma histology and relapsed as frequently as EPN-PFB, despite the supposed benign nature. Gross total resection and radiotherapy may represent key factors in determining the outcome of EPN-PFB patients.
2023-02-21 | GSE224218 | GEO
Project description:BackgroundA methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain unclear. Here, we retrospectively evaluate the impact of surgery and radiotherapy on outcome after molecular reclassification of adult intracranial ependymomas.MethodsTumors diagnosed as intracranial ependymomas from 170 adult patients collected from 8 diagnostic institutions were subjected to DNA methylation profiling. Molecular classes, patient characteristics, and treatment were correlated with progression-free survival (PFS).ResultsThe classifier indicated an ependymal tumor in 73.5%, a different tumor entity in 10.6%, and non-classifiable tumors in 15.9% of cases, respectively. The most prevalent molecular classes were posterior fossa ependymoma group B (EPN-PFB, 32.9%), posterior fossa subependymoma (PF-SE, 25.9%), and supratentorial ZFTA fusion-positive ependymoma (EPN-ZFTA, 11.2%). With a median follow-up of 60.0 months, the 5- and 10-year-PFS rates were 64.5% and 41.8% for EPN-PFB, 67.4% and 45.2% for PF-SE, and 60.3% and 60.3% for EPN-ZFTA. In EPN-PFB, but not in other molecular classes, gross total resection (GTR) (P = .009) and postoperative radiotherapy (P = .007) were significantly associated with improved PFS in multivariable analysis. Histological tumor grading (WHO 2 vs. 3) was not a predictor of the prognosis within molecularly defined ependymoma classes.ConclusionsDNA methylation profiling improves diagnostic accuracy and risk stratification in adult intracranial ependymoma. The molecular class of PF-SE is unexpectedly prevalent among adult tumors with ependymoma histology and relapsed as frequently as EPN-PFB, despite the supposed benign nature. GTR and radiotherapy may represent key factors in determining the outcome of EPN-PFB patients.
| S-EPMC10326475 | biostudies-literature
Project description:Whole-genome transcriptional profiling of human ependymoma tumors. Subgrouping based on mRNA expression profile. Fresh frozen tumor material was collected during tumor resection. Gene expression profiles illustrate distinct expression pattern at diagnosis.
2011-08-14 | E-GEOD-27283 | biostudies-arrayexpress
Project description:Background: The high incidence of recurrence and unpredictable clinical outcome for paediatric ependymoma reflect the imprecision of current therapeutic staging and need for novel risk stratification markers. Gain of chromosome 1q has been reported as a frequent aberration and correlate of adverse outcome in ependymoma. We therefore evaluated a prognostic role for 1q25 gain across three age-defined European clinical trial cohorts of paediatric intracranial ependymoma. Methods: The frequency of 1q gain in paediatric ependymoma was assessed across 51 tumours (42 primary, 9 recurrent) using Affymetrix® 500K SNP arrays. Gain of 1q25 was evaluated by interphase FISH (iFISH) across 189 primary intracranial ependymomas from children treated on the CCLG/SIOP CNS9204 (n = 60) and BBSFOP (n = 65) adjuvant chemotherapy trials, or with primary post-operative radiotherapy (SIOP CNS9904/RT group, n = 64). Results were correlated with clinical, histological and survival data. Findings: Gain of 1q was the most frequent imbalance in primary (7/42, 17 %) and recurrent ependymomas (3/9, 33 %). Gain of 1q25 was the strongest independent predictor of tumour progression in both CNS9204 (HR 3·36, p = 0·0009) and BBSFOP (HR 4·10, p = 0·0009) trial cohorts. In contrast, 1q25 gain was not prognostic for the older CNS9904/RT only group (PFS: p = 0·37, OS: p = 0·95). Clinical variables implicated in adverse outcome amongst cohorts included incomplete tumour resection and posterior fossa location. Interpretation: This is the first study to prospectively identify then validate a prognostic genomic marker for childhood ependymoma across independent prospective trial groups. 1q25 gain predicts progression in primary chemotherapy cohorts but not those treated by post-operative radiotherapy. We propose 1q25 gain is incorporated as an adverse marker into future European chemotherapeutic clinical trial design. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from flash frozen tumour specimens and patient-matched peripheral blood Copy number analysis of Affymetrix 500K SNP arrays was performed for DNA from 51 ependymomas and 40 constitutional DNA samples. Analysing broad genomic aberrations in 51 paediatric ependymomas, looking particularly at 1q gain.
2012-02-09 | E-GEOD-32101 | biostudies-arrayexpress
Project description:Goal of the experiment : Recurrence is a frequent phenomenon in intracranial childhood ependymomas. To understand this process, we investigated whether the gene expression profiling of matched ependymomas at diagnosis and at relapse could reveal key molecular events involved in tumor progression. To gain new insight in this process and identify mechanisms associated with recurrence, we compared the CGH profiles of local recurrences with the corresponding initial tumors. Brief description We analyzed 17 tumor samples at diagnosis and a total of 27 paired recurrences. Recurrences analyzed occurred after surgery only in 12 cases, surgery plus chemotherapy only in 9 cases and any treatment plus radiotherapy in 6 cases. We compared the level of CGH profile for each tumor at diagnosis and recurrence relative to normal commercial DNA using Agilent 4x44K Human CGH microarrays.
2011-06-20 | E-TABM-1023 | biostudies-arrayexpress
Project description:microRNA signatures with diagnosis, distant metastasis and prognosis for nasopharyngeal carcinoma
2012-05-10 | GSE36682 | GEO
Project description:Intracranial pediatric germ cell tumors (GCTs) have different histological differentiations, prognosis and clinical behaviors. Prognosis of patients with germinoma and mature teratoma is good, while patients with other types of GCTs, termed as nongerminomatous malignant germ cell tumors (NGMGCTs), require more extensive drug and irradiation treatment regimen. The mechanisms underlying different prognosis of various GCT subgroups remain elusive. We presented the first miRNA profile of pediatric primary intracranial GCTs.
2010-02-26 | GSE19347 | GEO
Project description:Background: The high incidence of recurrence and unpredictable clinical outcome for paediatric ependymoma reflect the imprecision of current therapeutic staging and need for novel risk stratification markers. Gain of chromosome 1q has been reported as a frequent aberration and correlate of adverse outcome in ependymoma. We therefore evaluated a prognostic role for 1q25 gain across three age-defined European clinical trial cohorts of paediatric intracranial ependymoma. Methods: The frequency of 1q gain in paediatric ependymoma was assessed across 51 tumours (42 primary, 9 recurrent) using Affymetrix® 500K SNP arrays. Gain of 1q25 was evaluated by interphase FISH (iFISH) across 189 primary intracranial ependymomas from children treated on the CCLG/SIOP CNS9204 (n = 60) and BBSFOP (n = 65) adjuvant chemotherapy trials, or with primary post-operative radiotherapy (SIOP CNS9904/RT group, n = 64). Results were correlated with clinical, histological and survival data. Findings: Gain of 1q was the most frequent imbalance in primary (7/42, 17 %) and recurrent ependymomas (3/9, 33 %). Gain of 1q25 was the strongest independent predictor of tumour progression in both CNS9204 (HR 3·36, p = 0·0009) and BBSFOP (HR 4·10, p = 0·0009) trial cohorts. In contrast, 1q25 gain was not prognostic for the older CNS9904/RT only group (PFS: p = 0·37, OS: p = 0·95). Clinical variables implicated in adverse outcome amongst cohorts included incomplete tumour resection and posterior fossa location. Interpretation: This is the first study to prospectively identify then validate a prognostic genomic marker for childhood ependymoma across independent prospective trial groups. 1q25 gain predicts progression in primary chemotherapy cohorts but not those treated by post-operative radiotherapy. We propose 1q25 gain is incorporated as an adverse marker into future European chemotherapeutic clinical trial design.
2012-02-09 | GSE32101 | GEO
Project description:microRNA signatures with diagnosis, distant metastasis and prognosis for nasopharyngeal carcinoma 62 nasopharyngeal carcinoma and 6 non-cancer nasopharyngitis fresh tissues were detected by microRNA microarray
2012-05-09 | E-GEOD-36682 | biostudies-arrayexpress
Project description:Despite extensively growing knowledge on the molecular biology of ependymoma, effective treatments are still lacking for about half patients with high-risk tumors. By applying single cell RNA-sequencing, we comprehensively identify a cellular hierarchy within ependymoma spanning undifferentiated and differentiated tumor cell states across all major molecular groups. This not only refines the concept of these established molecular groups but moreover provides a biological context for the well-known capacity of aggressive ependymomas for late recurrence and treatment resistance. Our newly defined transcriptomic signatures also prove to be of prognostic relevance within established high-risk ependymoma groups. Consequently, the newly characterized cell states could serve as promising future therapeutic targets and biomarkers for clinical trials.
2020-07-13 | GSE141460 | GEO