scholarly journals Preliminary observations on genetic alterations in pilocytic astrocytomas associated with neurofibromatosis 1

2003 ◽  
Vol 5 (4) ◽  
pp. 228-234 ◽  
Author(s):  
Kenji Tada ◽  
Masato Kochi ◽  
Hideyuki Saya ◽  
Jun-ichi Kuratsu ◽  
Shoji Shiraishi ◽  
...  
Keyword(s):  
Genetic Alterations ◽  
Neurofibromatosis 1 ◽  
Pilocytic Astrocytomas

scholarly journals PATH-22. COMPREHENSIVE ANALYSIS OF DIVERSE LOW-GRADE NEUROEPITHELIAL TUMORS WITH FGFR1 ALTERATIONS REVEALS A DISTINCT MOLECULAR SIGNATURE OF ROSETTE-FORMING GLIONEURONAL TUMOR

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii168-ii169
Author(s):  
Calixto-Hope G Lucas ◽  
Rohit Gupta ◽  
Pamela Doo ◽  
Matthew Wood ◽  
Marjorie Grafe ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tandem Duplication ◽  
Kinase Domain ◽  
Genetic Alterations ◽  
Glioneuronal Tumor ◽  
Tyrosine Kinase Domain ◽  
Low Grade ◽  
Missense Mutations ◽  
Ptpn11 Mutation ◽  
Pilocytic Astrocytomas

Abstract 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 (PA), 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 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, nor are the histopathologic features of pilocytic astrocytomas with FGFR1 alterations versus those harboring the more common BRAF mutations or fusions. 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 PA 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 refines the classification and histopathologic spectrum of LGNET with FGFR1 alterations.

scholarly journals LGG-13. PILOCYTIC ASTROCYTOMAS WITH NOVEL BRAF FUSIONS DEMONSTRATE MAPK PATHWAY ACTIVATION

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i34-i34
Author(s):  
Hannah Chatwin ◽  
Katherine Lind ◽  
John DeSisto ◽  
Bridget Sanford ◽  
Ahmed Gilani ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Genetic Alterations ◽  
Positive Control ◽  
Negative Control ◽  
Gene Set Enrichment Analysis ◽  
Low Grade ◽  
Normal Brain ◽  
Pilocytic Astrocytomas ◽  
Negative Controls ◽  
Control Samples

Abstract Background Pilocytic astrocytomas (PAs) are the most common pediatric low-grade glioma subtype. Oftentimes, PAs demonstrate somatic genetic alterations, the most common being the BRAF-KIAA1549 fusion, which results in constitutive activation of the MAPK pathway. Better understanding of the effects of other RAF fusions is necessary to determine the potential utility of MAPK-targeting therapies. Methods Three patients presented to Children’s Hospital Colorado and were ultimately diagnosed with PAs harboring previously unreported gene fusions identified as FYCO-RAF1, CCTTNNBP2-BRAF, and SLC44A1-BRAF. Utilizing immunohistochemistry, we stained novel samples and controls for ERK and pERK (phosphorylated ERK) to assess the activation of the MAPK pathway. PAs with known BRAF-KIAA1549 fusions (4 samples) and normal brain tissue (5 samples) were used as positive and negative controls, respectively. We additionally performed RNA sequencing to better understand expression changes associated with these fusions, utilizing Metascape and GSEA (Gene Set Enrichment Analysis) for analysis. Results Immunohistochemistry of negative control samples demonstrated less p-ERK than ERK (ratios of 0.6–0.9, mean 0.8). All samples with novel fusions demonstrated statistically significantly higher p-ERK expression compared to negative controls (ratios of 1.3–1.7, mean 1.4). These experimental samples also all fell within the p-ERK to ERK expression range of the positive control samples, which demonstrated the widest range of expression (ratios of 1.1–4.5, mean 2.2). Our molecular analysis further confirmed these results, with GSEA demonstrating positively upregulated MAPK and ERK pathways in 2 positive controls and 1 novel fusion sample. Metascape analysis emphasized overall similar gene expression between these samples, demonstrating many shared genes and functional pathways. Conclusions We identified 3 previously unreported RAF fusions in PA that demonstrate activation of the MAPK pathway, although not as extensively as seen in some positive control samples with BRAF-KIAA1549 fusions. MEK inhibition may be a useful therapeutic strategy in these tumors if targeted therapy is indicated.

Loss of neurofibromatosis 1 (NF1 ) gene expression in NF1-associated pilocytic astrocytomas

2000 ◽  
Vol 26 (4) ◽  
pp. 361-367 ◽  
Author(s):  
D. H. Gutmann ◽  
J. Donahoe ◽  
T. Brown ◽  
C. D. James ◽  
A. Perry
Keyword(s):  
Gene Expression ◽  
Neurofibromatosis 1 ◽  
Pilocytic Astrocytomas ◽  
Nf1 Gene

High performance Nanogold™-in situ hybridzation and its use in the detection of hybridized and PCR-amplified microscopical preparations

1996 ◽  
Vol 54 ◽  
pp. 896-897
Author(s):  
G. W. Hacker ◽  
I. Zehbe ◽  
J. Hainfeld ◽  
A.-H. Graf ◽  
C. Hauser-Kronberger ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Messenger Rna ◽  
High Performance ◽  
Detection System ◽  
Direct Methods ◽  
Genetic Alterations ◽  
Chain Reaction ◽  
Protein Encoding ◽  
Polymerase Chain

In situ hybridization (ISH) with biotin-labeled probes is increasingly used in histology, histopathology and molecular biology, to detect genetic nucleic acid sequences of interest, such as viruses, genetic alterations and peptide-/protein-encoding messenger RNA (mRNA). In situ polymerase chain reaction (PCR) (PCR in situ hybridization = PISH) and the new in situ self-sustained sequence replication-based amplification (3SR) method even allow the detection of single copies of DNA or RNA in cytological and histological material. However, there is a number of considerable problems with the in situ PCR methods available today: False positives due to mis-priming of DNA breakdown products contained in several types of cells causing non-specific incorporation of label in direct methods, and re-diffusion artefacts of amplicons into previously negative cells have been observed. To avoid these problems, super-sensitive ISH procedures can be used, and it is well known that the sensitivity and outcome of these methods partially depend on the detection system used.

Molecular genetic markers for thyroid FNAB

2015 ◽  
Vol 54 (03) ◽  
pp. 94-100 ◽  
Author(s):  
P. B. Musholt ◽  
T. J. Musholt
Keyword(s):  
Genetic Markers ◽  
Thyroid Nodules ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Diagnostic Tools ◽  
Ultrasound Screening ◽  
Thyroid Malignancy ◽  
Thyroid Carcinomas ◽  
Molecular Genetic Markers ◽  
The Impact

SummaryAim: Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18–65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Methods: Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Results: Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Conclusion: Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

Neuro-Optometric Treatment of Complications from a Cerebellar Astrocytoma

2020 ◽  
pp. 304-312
Keyword(s):  
Visual System ◽  
Common Site ◽  
Us Army ◽  
Cranial Nerve Palsies ◽  
Pilocytic Astrocytomas ◽  
The Us ◽  
Extent Of Damage ◽  
Functional Components ◽  
The Brain

Background: Insult to the brain, whether from trauma or other etiologies, can have a devastating effect on an individual. Symptoms can be many and varied, depending on the location and extent of damage. This presentation can be a challenge to the optometrist charged with treating the sequelae of this event as multiple functional components of the visual system can be affected. Case Report: This paper describes the diagnosis and subsequent ophthalmic management of an acquired brain injury in a 22 year old male on active duty in the US Army. After developing acute neurological symptoms, the patient was diagnosed with a pilocytic astrocytoma of the cerebellum. Emergent neurosurgery to treat the neoplasm resulted in iatrogenic cranial nerve palsies and a hemispheric syndrome. Over the next 18 months, he was managed by a series of providers, including a strabismus surgeon, until presenting to our clinic. Lenses, prism, and in-office and out-of-office neurooptometric rehabilitation therapy were utilized to improve his functioning and make progress towards his goals. Conclusions: Pilocytic astrocytomas are the most common primary brain tumors, and the vast majority are benign with excellent surgical prognosis. Although the most common site is the cerebellum, the visual pathway is also frequently affected. If the eye or visual system is affected, optometrists have the ability to drastically improve quality of life with neuro-optometric rehabilitation.

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