Genetic alterations in a papillary glioneuronal tumor

2008 ◽  
Vol 1 (1) ◽  
pp. 99-102 ◽  
Author(s):  
Claudia Faria ◽  
José Miguéns ◽  
João Lobo Antunes ◽  
Cândida Barroso ◽  
José Pimentel ◽  
...  
Keyword(s):  
Genetic Alterations ◽  
Point Of View ◽  
Chromosome 7 ◽  
Glioneuronal Tumor ◽  
Comparative Genomic ◽  
Low Grade ◽  
The Central Nervous System ◽  
High Level ◽  
Glioneuronal Tumors

✓Papillary glioneuronal tumors (PGNTs) are rare lesions of the central nervous system, and no information exists on the genetic alterations in these neoplasms. The authors report on such a case in a child. Genetic studies revealed that the tumor was characterized by gains and structural alterations involving only chromosome 7 with breakpoints at 7p22. By using comparative genomic hybridization, the authors observed a high-level amplification region at 7p14~q12. Fluorescence in situ hybridization with a probe for EGFR revealed that this gene was not amplified. Similar to other patients with PGNTs, the patient in the present case fared well. From a genetic point of view the data in the present case are in accordance with previous findings of EGFR amplifications as uncommon in low-grade gliomas and gangliogliomas. Recurrent rearrangements of chromosome 7 have been noted in other mixed glioneuronal tumors. The data in this case suggest that genes located at chromosome 7 can also be involved in the pathogenesis of PGNT. In clinical terms it will be especially important to corroborate, through the analysis of further cases, the involvement of the chromosome 7p22 locus, a region where glial and neuronal linked genes (RAC1 and NXPH1) are known to be located.

scholarly journals Detection and Correlation of Single and Concomitant TP53, PTEN, and CDKN2A Alterations in Gliomas

2019 ◽  
Vol 20 (11) ◽  
pp. 2658 ◽  
Author(s):  
Igor Andrade Pessôa ◽  
Carolina Koury Amorim ◽  
Wallax Augusto Silva Ferreira ◽  
Fernanda Sagica ◽  
José Reginaldo Brito ◽  
...  
Keyword(s):  
Tumor Suppressor Genes ◽  
Genetic Alterations ◽  
Comparative Genomic ◽  
Low Grade ◽  
Heterozygous Deletion ◽  
Single Strand Conformational Polymorphism ◽  
Primary Tumors ◽  
Tumor Subtypes ◽  
Frequent Event

Gliomas are the most frequent primary tumors of central nervous system and represent a heterogeneous group of tumors that originates from the glial cells. TP53, PTEN, and CDKN2A are important tumor suppressor genes that encode proteins involved in sustaining cellular homeostasis by different signaling pathways. Though genetic alterations in these genes play a significant role in tumorigenesis, few studies are available regarding the incidence and relation of concomitant TP53, PTEN, and CDKN2A alterations in gliomas. The purpose of this study was to evaluate the occurrence of mutation and deletion in these genes, through single-strand conformational polymorphism, array-comparative genomic hybridization, and fluorescence in situ hybridization techniques, in 69 gliomas samples. Molecular results demonstrated a significant higher prevalence of TP53, PTEN, and CDKN2A alterations in astrocytoma than other tumor subtypes, and heterozygous deletion was the most frequent event. In addition, a significant association was observed between TP53 and CDKN2A alterations (p = 0.0424), which tend to coexist in low grade astrocytomas (5/46 cases (10.9%)), suggesting that they are early events in development of these tumors, and PTEN and CDKN2A deletions (p = 0.0022), which occurred concomitantly in 9/50 (18%) patients, with CDKN2A changes preceding PTEN deletions, present preferably in high-grade gliomas.

scholarly journals A Biphasic Pleural Tumor with Features of an Epithelioid and Small Cell Mesothelioma: Morphologic and Molecular Findings

2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Sarah Hackman ◽  
Richard D. Hammer ◽  
Lester Layfield
Keyword(s):  
Abdominal Cavity ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Small Cell ◽  
Comparative Genomic ◽  
Cell Nuclei ◽  
Pleural Tumor ◽  
Young Males ◽  
Round Cell Tumors

Malignant mesotheliomas are generally classified into epithelioid, sarcomatoid, desmoplastic, and biphasic types with rare reports of a small cell form. These small cell variants display some morphologic overlap with desmoplastic small round cell tumors (DSRCTs) which generally occur within the abdominal cavity of young males and are defined by a characteristic t(11;22)(p13;q12) translocation. However, there are rare reports of DSRCTs lacking this translocation. We present a 78-year-old man with a pleura-based biphasic neoplasm with features of both epithelioid mesothelioma and a small cell blastema-like neoplasm. The epithelioid portion showed IHC reactivity for pan cytokeratin, CK5/6, D2-40, and calretinin and the small cell portion marked with CD99, pan cytokeratin, WT1, FLI1, S100, CD200, MyoD1, and CD15. Fluorescence in situ hybridization testing for the t(11;22)(p13;q12) translocation disclosed loss of theEWSR1gene in 94% of tumor cell nuclei, but there was no evidence of the classic translocation. Array based-comparative genomic hybridization (a-CGH) confirmed the tumor had numerous chromosome copy number losses, including 11p15.5-p11.12 and 22q12.1-q13.33, with loss of theEWSR1andWT1gene regions. Herein, we report novel complex CGH findings in a biphasic tumor and review the molecular genetic alterations in both mesothelioma and DSRCTs.

Organization and expression of the chicken N-myc gene

1990 ◽  
Vol 10 (5) ◽  
pp. 2017-2026
Author(s):  
S Sawai ◽  
K Kato ◽  
Y Wakamatsu ◽  
H Kondoh
Keyword(s):  
Genomic Sequence ◽  
Amino Acid Sequences ◽  
Coding Regions ◽  
Noncoding Exon ◽  
Exon 1 ◽  
Myc Gene ◽  
The Central Nervous System ◽  
Flanking Region ◽  
High Level

We cloned the chicken N-myc gene and analyzed its structure and expression. We found that it consisted of three exons with coding regions in exons 2 and 3. Comparison to mammalian N-myc genomic sequence indicated that nucleotide sequences of the 5'-flanking region, noncoding exon 1, and introns were not conserved, but coding and 3' noncoding sequences showed significant homology to mammalian N-myc. Alignment of deduced amino acid sequences of chicken and mammalian N-myc proteins revealed nine conserved domains interrupted by different lengths of nonhomologous sequences. Two of the domains were specific to N-myc proteins, and the other seven were common to c-myc proteins. Northern blot (immunoblot) and in situ hybridization analyses of 3.5-day-old chicken embryos revealed that high-level expression of the N-myc gene was confirmed to certain tissues, e.g., the central nervous system, neural crest derivatives, and mesenchyme of limb buds. In the beak and limb primordia, N-myc expression in the mesenchyme was higher toward the distal end, suggesting possible involvement in positional assignment of the tissue within the rudimentary structures.

scholarly journals Rosette-forming Glioneuronal Tumors in the Posterior Third Ventricle

2013 ◽  
Vol 40 (6) ◽  
pp. 885-888 ◽  
Author(s):  
Ibrahim Alnaami ◽  
Keith Aronyk ◽  
Jian-Qiang Lu ◽  
Edward S. Johnson ◽  
Cian O'Kelly
Keyword(s):  
Third Ventricle ◽  
Case Series ◽  
Neurofibromatosis Type ◽  
Pineal Region ◽  
World Health ◽  
Glioneuronal Tumor ◽  
First Case ◽  
The Central Nervous System ◽  
Health Organization ◽  
Glioneuronal Tumors

Rosette-forming glioneuronal tumor (RGNT) is a rare brain tumor found almost exclusively within the fourth ventricle. These grade I tumors were first included in the World Health Organization (WHO) Classification for the central nervous system in 20071. Since then, approximately 49 cases have been published.There are no reported cases of RGNT within the third ventricle, although this tumor has also been described in the pineal region, the tectum and within the aqueduct. Supratentorial localization is quite rare, with only three published: one was found in the septum pellucidum, another within the optic nerve in neurofibromatosis type 1 (NF1) patient and one in a patient with multiple RGNT in the lateral ventricle. The authors report the first case series in the literature of RGNT occurring within the posterior third ventricle.

scholarly journals LGG-06. COMPREHENSIVE GENOMIC CHARACTERIZATION AND INTEGRATED CLINICAL ANALYSIS OF LOW-GRADE GLIOMAS IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i32-i32
Author(s):  
Michael Fisher ◽  
David Jones ◽  
Yimei Li ◽  
Xiaofan Guo ◽  
Poonam Sonawane ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Pik3ca Mutation ◽  
Neurofibromatosis Type ◽  
Clinical Analysis ◽  
Genetic Alterations ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Fgfr1 Mutation ◽  
Glioneuronal Tumors

Abstract Background Low-grade gliomas (LGGs) arising in children with neurofibromatosis type 1 (NF1) are usually not biopsied. To identify secondary genetic alterations or molecular features that may contribute to pathogenesis and correlate with clinical behavior, we initiated a comprehensive molecular and clinical analysis of pediatric NF1-LGGs. Methods NF1-LGGs were analysed by whole-genome sequencing (31), targeted gene panel sequencing (9), RNAseq transcriptomal profiling (33) and genome-wide DNA methylation analysis (67). Clinical annotation was available for 48 subjects. Results Most LGGs harbored bi-allelic NF1 inactivation as the sole genetic abnormality, but 11% had additional alterations (FGFR1 mutation, n=3; PIK3CA mutation, n=2; homozygous 9p21 deletion, n=2; MYB:QKI fusion, n=1; SETD2 mutation, n=1; EGFR amplification, n=1). FGFR1 mutation conferred additional growth advantage in multiple complementary murine Nf1 models. 88% of NF1-LGGs resembled sporadic pilocytic astrocytoma (PA) by methylation, higher than that based on histology. Non-PA methylation patterns included low-grade glial/glioneuronal tumors, rosette-forming glioneuronal tumors, MYB/MYBL1-altered glioma, and high-grade astrocytoma with piloid features (2 tumors histologically diagnosed as LGG). In total, 18% of samples were classified as non-PA and/or harbored an additional non-NF1 mutation. Non-PA methylation class tumors were more likely to harbor an additional non-NF1 mutation (p=0.005). 7.7% of optic pathway hypothalamic gliomas (OPHGs) had other mutations or were not classified by methylation as PA, compared with 20.6% of NF1-LGGs arising elsewhere. There was no difference based on age for the presence of an additional non-NF1 mutation or non-PA methylation class. Conclusions Given the overall low occurrence of non-NF1 mutations or non-PA methylation class tumors in this series, routine clinical biopsy of typically-appearing NF1-LGG may not be indicated, particularly for children with OPHG. Biopsy should be considered for non-OPHG tumors refractory to conventional treatment. As additional agents are developed and treatment strategies evolve, the rationale for biopsy of NF1-LGG may become stronger.

scholarly journals Low-Grade Gliomas in Patients with Noonan Syndrome: Case-Based Review of the Literature

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 582
Author(s):  
Mariachiara Lodi ◽  
Luigi Boccuto ◽  
Andrea Carai ◽  
Antonella Cacchione ◽  
Evelina Miele ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Noonan Syndrome ◽  
Positive Outcome ◽  
Point Of View ◽  
Optic Pathway Glioma ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Solid Malignancies

Noonan syndrome (NS) is a congenital autosomic dominant condition characterized by a variable spectrum from a clinical and genetical point of view. Germline mutations in more than ten genes involved in RAS–MAPK signal pathway have been demonstrated to cause the disease. An higher risk for leukemia and solid malignancies, including brain tumors, is related to NS. A review of the published literature concerning low grade gliomas (LGGs) in NS is presented. We described also a 13-year-old girl with NS associated with a recurrent mutation in PTPN11, who developed three different types of brain tumors, i.e., an optic pathway glioma, a glioneuronal neoplasm of the left temporal lobe and a cerebellar pilocytic astrocytoma. Molecular characterization of the glioneuronal tumor allowed to detect high levels of phosphorylated MTOR (pMTOR); therefore, a therapeutic approach based on an mTOR inhibitor (everolimus) was elected. The treatment was well tolerated and proved to be effective, leading to a stabilization of the tumor, which was surgical removed. The positive outcome of the present case suggests considering this approach for patients with RASopathies and brain tumors with hyperactivated MTOR signaling.

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.

Rosette-Forming Glioneuronal Tumor in the Pineal Region: A Series of 6 Cases and Literature Review

2021 ◽  
Author(s):  
Chun-Chieh Lin ◽  
Mahesh M Mansukhani ◽  
Jeffrey N Bruce ◽  
Peter Canoll ◽  
George Zanazzi
Keyword(s):  
New York ◽  
Medical Center ◽  
Germ Cell Tumors ◽  
Genetic Alterations ◽  
Pineal Region ◽  
Tumor Formation ◽  
Mitogen Activated Protein Kinase ◽  
Small Cells ◽  
Glioneuronal Tumor ◽  
Low Grade

Abstract Resected lesions from the pineal region are rare specimens encountered by surgical pathologists, and their heterogeneity can pose significant diagnostic challenges. Here, we reviewed 221 pineal region lesions resected at New York-Presbyterian Hospital/Columbia University Irving Medical Center from 1994 to 2019 and found the most common entities to be pineal parenchymal tumors (25.3%), glial neoplasms (18.6%), and germ cell tumors (17.6%) in this predominantly adult cohort of patients. Six cases of a rare midline entity usually found exclusively in the fourth ventricle, the rosette-forming glioneuronal tumor, were identified. These tumors exhibit biphasic morphology, with a component resembling pilocytic astrocytoma admixed with variable numbers of small cells forming compact rosettes and perivascular pseudorosettes. Targeted sequencing revealed a 100% co-occurrence of novel and previously described genetic alterations in the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathways, suggesting a synergistic role in tumor formation. The most common recurrent mutation, PIK3CA H1047R, was identified in tumor cells forming rosettes and perivascular pseudorosettes. A review of the literature revealed 16 additional cases of rosette-forming glioneuronal tumors in the pineal region. Although rare, this distinctive low-grade tumor warrants consideration in the differential diagnosis of pineal region lesions.

Anaplastic Glioneuronal Tumor With KIAA1549/BRAF Fusion

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S102-S102
Author(s):  
Zhenggang Xiong ◽  
Prithvi Narayan
Keyword(s):  
Neoplastic Cell ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
High Grade ◽  
Left Frontal Lobe ◽  
Ki 67 ◽  
Blurry Vision ◽  
Immunohistochemical Assessment ◽  
Braf Fusion ◽  
Glioneuronal Tumors

Abstract Introduction Glioneuronal tumors are usually low grade and have a favorable prognosis. The anaplastic glioneuronal tumor with KIAA1549/BRAF fusion has not yet been documented. This article reports a pediatric case of glioneuronal tumor with anaplasia and KIAA1549/BRAF fusion to illuminate the importance of KIAA1549/BRAF fusion in the tumorigenesis and clinical management of high-grade glioneuronal tumors. Case Presentation A 10-year-old boy presented with 1 year of headache and 3 months of blurry vision and proptosis. Ophthalmologic evaluation revealed bilateral papilledema. Magnetic resonance imaging showed a large mixed cystic and solid mass in the left frontal lobe of cerebrum. Histologic analysis demonstrated a glioneuronal tumor with papillary/pseudopapillary growth pattern, focal necrosis, microcalcification, and brisk mitotic activity with a high Ki-67 labeling index of focally up to 20%. Immunohistochemical assessment identified a mixed glial and neuronal neoplastic cell population. Molecular studies revealed a KIAA1549/BRAF fusion. Conclusion KIAA1549/BRAF fusion may play an important role in the oncogenesis of high-grade glioneuronal tumors. In view of the fact that effective, targeted therapies for the tumors with KIAA1549/BRAF fusion are clinically available, detection of KIAA1549/BRAF fusion for glioneuronal tumors, particularly high-grade glioneuronal tumors, is helpful.

Recurrent involvement of the REL and BCL11Aloci in classical Hodgkin lymphoma

Blood ◽  
2002 ◽  
Vol 99 (4) ◽  
pp. 1474-1477 ◽  
Author(s):  
José I. Martı́n-Subero ◽  
Stefan Gesk ◽  
Lana Harder ◽  
Takashi Sonoki ◽  
Philip W. Tucker ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Hodgkin Lymphoma ◽  
Copy Number ◽  
Chromosome Region ◽  
Comparative Genomic ◽  
Classical Hodgkin Lymphoma ◽  
Interphase Cytogenetics ◽  
High Level ◽  
Minimal Region

Comparative genomic hybridization studies have shown gains in chromosome region 2p as the most common imbalance in classical Hodgkin lymphoma (cHL). The minimal region of gain contained 2 candidate oncogenes, REL and BCL11A. This study examined the involvement of REL and BCL11A loci in 44 primary cases of cHL by combined immunophenotyping and interphase cytogenetics (FICTION). A median 2p13 copy number above the tetraploid range was detected in 24 (55%) cases. Adjustment for centromere 2 copy number indicated gains of 2p13 in 11 of 31 cHLs (35%) with 8 (26%) high-level amplifications. One cHL displayed selective amplification of the REL locus not affectingBCL11A; another case studied by FICTION and a cHL with cytogenetic 2p change investigated by fluorescence in situ hybridization showed signal patterns suggesting breakpoints in the region spanned by the REL probe. These data indicate thatREL rather than BCL11A may be the target of the 2p13 alterations in cHL.

Sign in / Sign up

Export Citation Format

Share Document