Combined Molecular Genetic Studies of Chromosome 22q and the Neurofibromatosis Type 2 Gene in Central Nervous System Tumors

Ng, Ho Keung; Lau, Kin‐Mang; Tse, Jenny; Lo, Kwok Wai; Wong, Joseph H. C.; Poon, Wai Sang; Huang, Dolly P.

doi:10.1227/00006123-199510000-00022

Cited by 52 publications

(5 citation statements)

References 52 publications

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“…Alternatively, such dysplastic abnormalities may represent random developmental events, without an environmental trigger. This raises the possibility of somatic mutations in genes critical for cortical development, as suggested for sporadic meningiomas where somatic mutations in the NF2 gene occur 23…”

Section: Discussionmentioning

confidence: 99%

Causes of epilepsies: Insights from discordant monozygous twins

et al. 2001

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Whereas some patients with epilepsy have known acquired or genetic causes, in many the cause is unknown. By analyzing monozygotic twins, discordant for epilepsy, subtle etiological factors may be detected. We analyzed 12 monozygotic, discordant twins for factors explaining discordancy. These factors were presence of major clinical risk factors, presence of possibly epileptogenic lesions on brain magnetic resonance imaging (MRI), and quantitative brain volume abnormalities. Major risk factors, with associated acquired lesions were found in 4 of 12 twins. An MRI lesion without a major risk factor was found in a further 4 of 12 twins. Two of these had unilateral malformations of cortical development, 1 had bilateral periventricular heterotopia, and 1 had focal atrophy. Significant twin–twin differences in MRI volumes without obvious MRI lesions or major risk factors were found in 2 of 12 twins. Both had larger volumes than their co‐twins, and idiopathic generalized epilepsy. No clinical or MRI findings accounting for discordance for epilepsy were found in 2 of 12 twins. In 10 of 12 pairs a clinical or MR correlate of epilepsy was found; some of those were subtle and only apparent by twin–twin comparison. They may be due to occult acquired factors, such as prenatal insults, or to genetic abnormalities resulting from postfertilization genetic processes. Ann Neurol 2001;49:45–52

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Section: Discussionmentioning

confidence: 99%

Causes of epilepsies: Insights from discordant monozygous twins

et al. 2001

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“…The pathogenesis of meningioma is a complex process associated with an accumulation of various genetic and epigenetic alterations that occur during the initiation and progression of the tumor ( 7 ). Monosomy 22, 22q deletion and/or mutation of the neurofibromatosis type 2 gene have been identified as important initiating events and represent the most common genetic alterations in meningiomas ( 8 – 10 ). Other common chromosomal alterations include deletions of 1p, 6q, 10q and 14q, and insertions of 1q, 9q, 12q, 15q, 17q and 20q ( 7 , 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of key genes and pathways in meningioma by bioinformatics analysis

Dai

Chu

et al. 2018

Oncol Lett

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Meningioma is the most frequently occurring type of brain tumor. The present study aimed to conduct a comprehensive bioinformatics analysis of key genes and relevant pathways involved in meningioma, and acquire further insight into the underlying molecular mechanisms. Initially, differentially expressed genes (DEGs) in 47 meningioma samples as compared with 4 normal meninges were identified. Subsequently, these DEGs were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. In addition, a protein-protein interaction (PPI) network of the identified DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes and visualized using Cytoscape. In total, 1,683 DEGs were identified, including 66 upregulated and 1,617 downregulated genes. The GO analysis results revealed that the DEGs were significantly associated with the ‘protein binding’, ‘cytoplasm’, ‘extracellular matrix (ECM) organization’ and ‘cell adhesion’ terms. The KEGG analysis results demonstrated the significant pathways included ‘AGE-RAGE signaling pathway in diabetic complications’, ‘PI3K-Akt signaling pathway’, ‘ECM-receptor interaction’ and ‘cell adhesion molecules’. The top five hub genes obtained from the PPI network were JUN, PIK3R1, FOS, AGT and MYC, and the most enriched KEGG pathways associated with the four obtained modules were ‘chemokine signaling pathway’, ‘cytokine-cytokine receptor interaction’, ‘allograft rejection’, and ‘complement and coagulation cascades’. In conclusion, bioinformatics analysis identified a number of potential biomarkers and relevant pathways that may represent key mechanisms involved in the development and progression of meningioma. However, these findings require verification in future experimental studies.

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“…For non‐ NF2 /22q tumors in this cohort, CDKN2A/B homozygous deletion, 1q gain, 3p loss, 18q loss and ALT were found to be common molecular changes developing in recurrences. Goutagny et al [ 13 ] also found a higher burden of cytogenetic alterations in NF2 ‐mutant meningiomas and Bi et al [ 6 ] showed similar findings among higher‐grades meningiomas with 22q loss. We appreciate that more than one locus may be gained or lost at a specific chromosomal arm.…”

Section: Discussionmentioning

confidence: 78%

“…Aetiologically, it has been known for a long time that neurofibromatosis type 2 ( NF2 ) gene located on chromosome 22q is lost or mutated in up to half of all meningiomas [ 2 , 11 , 12 , 13 ]. NF2 inactivation is regarded as an early event in meningiomagenesis [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular landscapes of longitudinal NF2/22q and non‐NF2/22q meningiomas show different life histories

Chung

et al. 2022

Brain Pathology

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Recurrence is a major complication of some meningiomas. Although there were many studies on biomarkers associated with higher grades or increased aggressiveness, few studies specifically examined longitudinal samples of primary meningiomas and recurrences from the same patients for molecular life history. We studied 99 primary and recurrent meningiomas from 42 patients by FISH for 22q, 1q, 1p, 3p, 5q, 6q, 10p, 10q, 14q, 18q, CDKN2A/B homozygous deletion, ALT (Alternative Lengthening of Telomere), TERT re‐arrangement, targeted sequencing and TERT p sequencing. Although NF2 mutation and 22q were well known to be aetiological events in meningiomas, we found that in these paired meningiomas, combining the two events resulted in an NF2 /22q group (57 tumors from 25 patients) which were almost mutually exclusive with those cases without these two changes (42 tumors from 17 patients) for NF2 /22q. No other molecular changes were totally unique to NF2 /22q or non‐ NF2 /22q tumors. For molecular evolution, NF2 /22q meningiomas had higher cytogenetic abnormalities than non‐ NF2 /22q meningiomas ( p = 0.003). Most of the cytogenetic changes in NF2/ 22q meningiomas were present from the outset whereas for non‐ NF2 /22q meningiomas, cytogenetic events were uncommon in the primary tumors and most were acquired in recurrences. For non‐ NF2 /22q tumors, CDKN2A/B homozygous deletion, 1q gain, 18p loss, 3p loss, and ALT were preferentially found in recurrences. Mutations were largely conserved between primary and recurrent tumors. Phylogenetic trees showed 11/11 patients with multiple recurrent tumors had a conserved evolutionary pattern. We conclude that for molecular life history, NF2 and 22q should be regarded as a group. NF2 /22q recurring meningiomas showed more cytogenetic abnormalities in the primary tumors, whereas non‐ NF2 /22q meningiomas showed CDKN2A/B deletion and other cytogenetic abnormalities and ALT at recurrences. Although chromosome 1p loss is a known poor prognostic marker in meningiomas, it was also associated with a shorter TBR (time between resection) in this cohort ( p = 0.002).

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Combined Molecular Genetic Studies of Chromosome 22q and the Neurofibromatosis Type 2 Gene in Central Nervous System Tumors

Cited by 52 publications

References 52 publications

Causes of epilepsies: Insights from discordant monozygous twins

Causes of epilepsies: Insights from discordant monozygous twins

Identification of key genes and pathways in meningioma by bioinformatics analysis

Molecular landscapes of longitudinal NF2/22q and non‐NF2/22q meningiomas show different life histories

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