Exploration of Involved Key Genes and Signaling Diversity in Brain Tumors

Nasser, Mojdeh Mahdian; Mehdipour, Parvin

doi:10.1007/s10571-017-0498-9

Cited by 19 publications

(17 citation statements)

References 156 publications

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“…A long‐scale study conducted by The Cancer Genome Atlas (TCGA) revealed numerous data on specific genetic and epigenetic alterations underlying gliomas . Although it is still not possible to define the exact number and chronology of changes during gliomagenesis, they found that key genes responsible for the formation and progression of astrocytic brain tumours are most frequently involved into deregulated oncogenic pathways: RTK/RAS/PI3K, TP53 and RB . Recent studies have shown that altered signal transduction in Wnt signalling pathway is also involved in the molecular pathogenesis of glial tumours …”

Section: Introductionmentioning

confidence: 99%

Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation

Kafka

Bačić²,

Tomas

et al. 2018

J Cellular Molecular Medi

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Key regulators of the Wnt signalling, DVL1, DVL2 and DVL3, in astrocytomas of different malignancy grades were investigated. Markers for DVL1,DVL2 and DVL3 were used to detect microsatellite instability (MSI) and gross deletions (LOH), while immunohistochemistry and immunoreactivity score were used to determine the signal strengths of the three DVL proteins and transcription factors of the pathway, TCF1 and LEF1. Our findings demonstrated that MSI at all three DVL loci was constantly found across tumour grades with the highest number in grade II (P = 0.008). Collectively, LOHs were more frequent in high‐grade tumours than in low grade ones. LOHs of DVL3 gene were significantly associated with grade IV tumours (P = 0.007). The results on protein expressions indicated that high‐grade tumours expressed less DVL1 protein as compared with low grade ones. A significant negative correlation was established between DVL1 expression and malignancy grades (P < 0.001). The expression of DVL2 protein was found similar across grades, while DVL3 expression significantly increased with malignancy grades (P < 0.001). The signal strengths of expressed DVL1 and DVL3 were negatively correlated (P = 0.002). However, TCF1 and LEF1 were both significantly upregulated and increasing with astrocytoma grades (P = 0.001). A positive correlation was established between DVL3 and both TCF1 (P = 0.020) and LEF1 (P = 0.006) suggesting their joint involvement in malignant progression. Our findings suggest that DVL1 and DVL2 may be involved during early stages of the disease, while DVL3 may have a role in later phases and together with TCF1 and LEF1 promotes the activation of Wnt signalling.

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Section: Introductionmentioning

confidence: 99%

Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation

Kafka

Bačić²,

Tomas

et al. 2018

J Cellular Molecular Medi

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“…Mechanism of long term resting state is unclear in brain tumors. 18) Recent report shows that Notch and WNT signaling pathway relates to cell cycle and re-activation of proliferation cycle in meningioma and astrocytoma. 18) Expression of these signaling factors might contribute to predict future recurrence and be useful as a marker of cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Non-contiguous Meningeal Recurrence of Olfactory Neuroblastoma: A Case Report and Literature Review

Saito

Sasaki

Inoue

et al. 2018

NMC Case Report Journal

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Olfactory neuroblastoma is an uncommon malignant tumor of neural crest origin arising from the olfactory epithelium of the superior nasal cavity. There are some reports of local recurrence or continuous extension along the olfactory epithelium to the central nervous system, but non-contiguous distant meningeal metastasis without local recurrence at the primary site is rare. We report a case of non-contiguous meningeal recurrence of olfactory neuroblastoma presenting as a giant frontal mass. A 66-year-old woman was admitted with a left nasal intranasal localized tumor without cranial extension and gross total removal was achieved. Pathological examination showed olfactory neuroblastoma and radiation therapy was added in a limited region of the removal cavity. Radiological follow-up continued for 10 years and there was no local recurrence. Sixteen years after radiation therapy, the patient found a slight frontal mass gradually growing. Magnetic resonance imaging revealed an enhanced mass lesion of 7 cm in thickness and 9 cm in diameter associated with marked thickness of the frontal bone, intradural cystic mass compressing the bilateral frontal lobe, and no local recurrence. A second operation was performed followed by radiotherapy and we diagnosed no-contiguous meningeal recurrence of metastatic olfactory neuroblastoma. Olfactory neuroblastoma is a locally aggressive tumor. Although metastasis of this tumor has been reported, non-contiguous spread to the dura is rare. Understanding the route of remote metastasis and careful evaluation after primary treatment are needed to avoid misdiagnosis and treatment delays.

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“…Bar charts were used to illustrate the number of genes that overlap in both KEGG pathways and functional annotation clusters. Moreover, dot matrices were computed to reflect the impact of genes associated with each KEGG pathway as well as enrichment maps and GSEA plots (Morgan et al, 2017). Matrix layout for all genes within 18 KEGG pathways sorted by size.…”

Section: Computation Analysis Of Cnasmentioning

confidence: 99%

Comparable genomic copy number aberrations differ across astrocytoma malignancy grades

Pećina‐Šlaus

Kafka

Jerčić

et al. 2018

Preprint

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Malignancy grades of astrocytomas were analyzed for copy number aberrations by aCGH. Altogether 1438 CNA were found of which losses prevailed. We searched for regions that are more likely to drive cancer pathogenesis with Bioconductor package and Genomic Identification of Significant Targets in Cancer. On our total sample significant deletions affected 14 chromosomal regions, out of which deletions at 17p13.2, 9p21.3, 13q12.11, 22q12.3 remained significant even at 0.05 q-value. When divided to malignancy groups, the regions identified as significantly deleted in high grades were: 9p21.3; 17p13.2; 10q24.2; 14q21.3; 1p36.11 and 13q12.11, while amplified were: 3q28; 12q13.3 and 21q22.3. Low grades comprised significant deletions at 3p14.3; 11p15.4; 15q15.1; 16q22.1; 20q11.22 and 22q12.3 indicating their involvement in early stages of tumorigenesis. Significantly enriched pathways brought by DAVID software were PI3K-Akt, Cytokine-cytokine receptor, NODlike receptor, Jak-STAT, RIG-II-like receptor and Toll-like receptor pathways. HPV and herpex simplex infection and inflammation pathways were also represented. Present study brings new data to astrocytoma research amplifying the wide spectrum of changes which could help us identify the regions critical for tumorigenesis. KeywordsAstrocytoma/aCGH/comparative genomic hybridization/Copy number aberrations/ GISTIC

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Exploration of Involved Key Genes and Signaling Diversity in Brain Tumors

Cited by 19 publications

References 156 publications

Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation

Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation

Non-contiguous Meningeal Recurrence of Olfactory Neuroblastoma: A Case Report and Literature Review

Comparable genomic copy number aberrations differ across astrocytoma malignancy grades

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