Low-grade glioneuronal tumors with FGFR2 fusion resolve into a single epigenetic group corresponding to 'Polymorphous low-grade neuroepithelial tumor of the young'.
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ABSTRACT:
SUBMITTER: Gupta R
PROVIDER: S-EPMC8357689 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
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Low-grade glioneuronal tumors with FGFR2 fusion resolve into a single epigenetic group corresponding to 'Polymorphous low-grade neuroepithelial tumor of the young'.
Gupta Rohit R Lucas Calixto-Hope G CG Wu Jasper J Barreto Jairo J Shah Kathan K Simon Iraide Bernal IB Casavilca-Zambrano Sandro S Brathwaite Carole C Zhou Holly H Caccamo Dario D Gilani Ahmed A Kleinschmidt-DeMasters Bette K BK Lee Julieann C JC Perry Arie A Clarke Jennifer L JL Chang Susan M SM Berger Mitchel S MS Solomon David A DA
Acta neuropathologica 20210728 3
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Project description:BackgroundPolymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described entity that can mimic high-grade glioma (HGG) in histologic and molecular features; however, factors predicting aggressive behavior in these tumors are unclear.MethodsWe present an indolent neuroepithelial neoplasm in a 59-year-old female with imaging initially suggestive of HGG, and a series of adult patients with HGG harboring FGFR3-TACC3 fusions are also presented for comparison.ResultsPathology in the case patient revealed low-grade cytomorphology, microcalcifications, unusual neovascularization, and a low proliferation index. The lesion was diffusely CD34+ and harbored an FGFR3-TACC3 fusion and TERT promoter mutation. A diagnosis of PLNTY was therefore favored and the patient was observed with no progression at 15-month follow-up. In patients with HGG with FGFR3-TACC3 fusions, molecular findings included IDH-wildtype status, absence of 1p19q codeletion, CDKN2A loss, TERT promoter mutations and lack of MGMT promoter methylation. These patients demonstrated a median 15-month overall survival and a 6-month progression-free survival.ConclusionPLNTY is a rare low-grade entity that can display characteristics of HGG, particularly in adults. Presence of FGFR3-TACC3 fusions and other high-grade features should raise concern for a more malignant precursor lesion when a diagnosis of PLNTY is considered.
| S-EPMC10698862 | biostudies-literature
Project description: Not available
| S-EPMC8493813 | biostudies-literature
Project description:BackgroundPolymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a low-grade epilepsy-associated tumor recently introduced in WHO 2021 classification. Since it has been recognized as an independent nosological entity, PLNTY has been mainly studied from a genetic and molecular perspective, not recognizing unique characteristic clinical and radiological features.MethodsA systematic literature research has been conducted aiming to identify all relevant studies about the radiological, clinical and surgical features of PLNTY. We described a representative case of a 45-year-old man treated with awake-surgery with confirmed diagnosis of PLNTY, reporting the radiological and surgical characteristics through imaging and intra-operative video. We performed a statistical meta-analysis attempting to assess the presence of relationships between surgical and radiologic tumor characteristics and clinical outcome and type of surgery.ResultsA total of 16 studies were included in the systematic review. The final cohort was composed of 51 patients. Extent of resection (EOR) and outcome are not significantly associated with the different genetic profiling (p = 1), the presence of cystic intralesional component, calcification (p = 0.85), contrast-enhancing and lesion boundaries (p = 0.82). No significant correlation there is between EOR and remission or better control of epilepsy-related symptoms (p = 0.38). The contrast enhancement in the tumor is significantly associated with recurrence or poor control of epileptic symptoms (p = 0.07).ConclusionsIn PLNTYs, contrast enhancement seems to impact prognosis, recurrence, and seizure control much more than radiological features, genetic features and type of resection of the tumor.
| S-EPMC10133071 | biostudies-literature
Project description:Genome-wide DNA methylation profiling of 8 low-grade neuroepithelial tumors (LGNET) with FGFR2 fusions with various histologic diagnoses including ganglioglioma, multinodular and vacuolating neuronal tumor (MVNT), low-grade glioneuronal tumor NOS, and polymorphous low-grade neuroepithelial tumor of the young (PLNTY). 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 of 8 low-grade neuroepithelial tumors with FGFR2 fusions.
2021-07-27 | GSE172081 | GEO
Project description:Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described epileptogenic tumor characterized by oligodendroglioma-like components, aberrant CD34 expression, and frequent mitogen-activated protein kinase (MAPK) pathway activation. We molecularly profiled 13 cases with diagnostic histopathological features of PLNTY (10 female; median age, 16 years; range, 5-52). Patients frequently presented with seizures (9 of 12 with available history) and temporal lobe tumors (9 of 13). MAPK pathway activating alterations were identified in all 13 cases. Fusions were present in the 7 youngest patients: FGFR2-CTNNA3 (n = 2), FGFR2-KIAA1598 (FGFR2-SHTN1) (n = 1), FGFR2-INA (n = 1), FGFR2-MPRIP (n = 1), QKI-NTRK2 (n = 1), and KIAA1549-BRAF (n = 1). BRAF V600E mutation was present in 6 patients (17 years or older). Two fusion-positive cases additionally harbored TP53/RB1 abnormalities suggesting biallelic inactivation. Copy number changes predominantly involving whole chromosomes were observed in all 10 evaluated cases, with losses of chromosome 10q occurring with FGFR2-KIAA1598 (SHTN1)/CTNNA3 fusions. The KIAA1549-BRAF and QKI-NTRK2 fusions were associated respectively with a 7q34 deletion and 9q21 duplication. This study shows that despite its name, PLNTY also occurs in older adults, who frequently show BRAF V600E mutation. It also expands the spectrum of the MAPK pathway activating alterations associated with PLNTY and demonstrates recurrent chromosomal copy number changes consistent with chromosomal instability.
| S-EPMC8921648 | biostudies-literature
Project description:We present a case of a 14-year old boy with tumor-associated refractory epilepsy. Positron emission tomography imaging demonstrated a region with heterogeneous high 11C-methionine uptake and a region with homogenous low 18F-fluorodeoxyglucose uptake within the tumor. Histopathological and genomic analyses confirmed the tumor as BRAF V600E-mutated polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Within the high-methionine-uptake region, we observed increased protein levels of L-type amino acid transporter 1 (LAT1), a major transporter of methionine; c-Myc; and constituents of the mitogen-activated protein kinase (MAPK) pathway. We also found that LAT1 expression was linked to the BRAF V600E mutation and subsequent activation of MAPK signaling and c-Myc. Pharmacological and genetic inhibition of the MAPK pathway suppressed c-Myc and LAT1 expression in BRAF V600E-mutated PLNTY and glioblastoma cells. The BRAF inhibitor dabrafenib moderately suppressed cell viability in PLNTY. Collectively, our results indicate that BRAF V600E mutation-activated MAPK signaling and downstream c-Myc induces specific metabolic alterations in PLNTY, and may represent an attractive target in the treatment of the disease.
| S-EPMC7436956 | biostudies-literature
Project description:AimsFGFR-fused central nervous system (CNS) tumours are rare and are usually within the glioneuronal and neuronal tumours or the paediatric-type diffuse low-grade glioma spectrum. Among this spectrum, FGFR2 fusion has been documented in tumours classified by DNA-methylation profiling as polymorphous low-grade neuroepithelial tumours of the young (PLNTY), a recently described tumour type. However, FGFR2 fusions have also been reported in glioneuronal tumours, highlighting the overlapping diagnostic criteria and challenges.MethodsWe investigated the FGFR2 fusion landscape in a French national series of tumours sent to the RENOCLIP-LOC network. We comprehensively analysed histology, radiology and molecular data including DNA-methylation profiling for 16 FGFR2-fused glioneuronal tumours.ResultsMost tumours were located in the temporal or parietal lobe with a median age at diagnosis of 7 years [1-44]. Epilepsy was the most frequent symptom. Five patients had tumour progression or recurrence with a median progression-free survival of 22.6 months. Histological phenotypes corresponding to PLNTY, GG, MVNT or unclassified tumours were recorded. Epigenetic profiling could not properly distinguish epigenetic clusters related to the GG and PLNTY methylation classes among FGFR2-fused glioneuronal tumours. However, a neuroradiological review identified strikingly distinct neuroradiological patterns.ConclusionWhile delineating tumour types among the FGFR2-fused glioneuronal tumour spectrum, by histopathology or DNA-methylation profiling, remains challenging, neuroimaging data revealed two distinct patterns that could correlate to PLNTY and ganglioglioma. However, more series including extensive histo-radio-molecular data are needed to confirm this hypothesis.
| S-EPMC11618513 | biostudies-literature
Project description:BACKGROUND:A new type of epileptogenic tumor, the polymorphous low-grade neuroepithelial tumor of the young (PLNTY) was firstly reported by Jason T. Huse et al. at 2016. After that, only 1 case of PLNTY was reported by article. The radiological characteristics of PLNTY have not been concluded. The objective of our study was to report 3 cases of PLNTYs in details and to analyze the image characteristics and genetic alterations of PLNTYs by reviewing our cases and articles. CASE PRESENTATION:There were 3 cases diagnosed as PLNTY by pathology in our hospital during the last 10?years, with the average age of 15. They were all suffered from different degrees of epilepsy. All of them underwent magnetic resonance (MR) imaging and 2 of them underwent computer tomography (CT) imaging. The PLNTYs are all appearing as a solid or solid-cystic cortical mass with little mass effect and unclear boundary with normal brain tissue. They are all shown as hyperintensity in T2WI and iso-/hypointensity in T1WI with slight or no enhancement after contract enhanced in MR imaging. The "salt and pepper sign" in T2WI and grit calcification in CT images might be specific characteristics of PLNTY. All of them recovered after excision of the tumors. The gene tests revealed fibroblast growth factor receptors 3 (FGFR3)-TACC3 fusion and FGFR3 amplification in one case, and the B-Raf proto-oncogene (BRAF) V600E mutation in another case. CONCLUSION:In the image, the partial ill-marginated cortical mass with "salt and pepper sign" in T2WI or grit calcification in CT imaging might be the typical imaging characteristics of PLNTY. We also prove that the BRAF V600E mutation as well as the FGFR2 and FGFR3 have a close relationship with PLNTY.
| S-EPMC7137220 | biostudies-literature
Project description:We present a case of de novo polymorphous low-grade adenocarcinoma (PLGA) arising in a minor salivary gland with a relatively large radiographic extent compared with that of most of the PLGAs reported. This paper describes the radiographic extent of the lesion and the findings of CT imaging.
| S-EPMC3699016 | biostudies-other
Project description:The FGFR1 gene encoding fibroblast growth factor receptor 1 has emerged as a frequently altered oncogene in the pathogenesis of multiple low-grade neuroepithelial tumor (LGNET) subtypes including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumor (DNT), rosette-forming glioneuronal tumor (RGNT), and extraventricular neurocytoma (EVN). These activating FGFR1 alterations in LGNET can include tandem duplication of the exons encoding the intracellular tyrosine kinase domain, in-frame gene fusions most often with TACC1 as the partner, or hotspot missense mutations within the tyrosine kinase domain (either at p.N546 or p.K656). However, the specificity of these different FGFR1 events for the various LGNET subtypes and accompanying genetic alterations are not well defined. Here we performed comprehensive genomic and epigenomic characterization on a diverse cohort of 30 LGNET with FGFR1 alterations. We identified that RGNT harbors a distinct epigenetic signature compared to other LGNET with FGFR1 alterations, and is uniquely characterized by FGFR1 kinase domain hotspot missense mutations in combination with either PIK3CA or PIK3R1 mutation, often with accompanying NF1 or PTPN11 mutation. In contrast, EVN harbors its own distinct epigenetic signature and is characterized by FGFR1-TACC1 fusion as the solitary pathogenic alteration. Additionally, DNT and pilocytic astrocytoma are characterized by either kinase domain tandem duplication or hotspot missense mutations, occasionally with accompanying NF1 or PTPN11 mutation, but lacking the accompanying PIK3CA or PIK3R1 mutation that characterizes RGNT. The glial component of LGNET with FGFR1 alterations typically has a predominantly oligodendroglial morphology, and many of the pilocytic astrocytomas with FGFR1 alterations lack the biphasic pattern, piloid processes, and Rosenthal fibers that characterize pilocytic astrocytomas with BRAF mutation or fusion. Together, this analysis improves the classification and histopathologic stratification of LGNET with FGFR1 alterations.
| S-EPMC7456392 | biostudies-literature