Characterization of novel CTNNB1 mutation in Craniopharyngioma by whole-genome sequencing

He, Jinzhi; Zeng, Zhen; Wang, Yuelong; Deng, Jiaojiao; Tang, Xin; Liu, Fujun; Huang, Jianhan; Chen, Hongxu; Liang, Ruichao; Zan, Xin; Li, Yong; Tong, Aiping; Guo, Gang; Xu, Jianguo; Zhu, Xiaofeng; Zhou, Liangxue; Peng, Yong

doi:10.1186/s12943-021-01468-7

Cited by 19 publications

(15 citation statements)

References 67 publications

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“…The latest study has confirmed that β-catenin nuclear stability activates the wnt-signaling pathway and promotes cell proliferation 41 . Our study also confirmed that the cyst wall has more β-catenin nuclear positive cells than the solid body, indicating that the cyst wall has a stronger proliferative capacity.…”

Section: Discussionmentioning

confidence: 98%

Molecular biological features of cyst wall of adamantinomatous craniopharyngioma

Chuan

Wang²,

Liu

et al. 2023

Sci Rep

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The molecular biological differences between cyst walls and those in solid bodies are the foundation of the outcomes. In this study, the CTNNB1 mutations were confirmed by DNAsequencing; CTNNB1 expression levels were detected by PCR; the differences between solid bodies and cyst walls in proliferative capacity and tumor stem cell niches were assessed by immunohistochemistry; the effect of the residual cyst wall on recurrence was assessed by follow-up. Mutations in the CTNNB1 in the cyst wall and the solid body were identical in each case. No differences were found in the transcriptional level of CTNNB1 between the cyst walls and the solid bodies (P = 0.7619). The cyst wall showed a pathological structure similar to the solid body. Proliferative capacity of cyst walls was stronger than that of solid body (P = 0.0021), and β-catenin nuclear positive cells (cell clusters) in cyst walls were more than that in solid tumor (P = 0.0002). The retrospective 45 ACPs showed residual cyst wall was significantly associated with tumor recurrence or regrowth (P = 0.0176). Kaplan–Meier analysis showed there was a significant difference in the prognosis between GTR and STR (P < 0.0001).The cyst wall of ACP contained more tumor stem cell niches which could lead to the recurrence. According to the above-mentioned, a special attention to the management of the cyst wall should be paid.

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Section: Discussionmentioning

confidence: 98%

Molecular biological features of cyst wall of adamantinomatous craniopharyngioma

Chuan

Wang²,

Liu

et al. 2023

Sci Rep

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“…The Wnt signaling pathway is an important aspect of ACP pathogenesis. CTNNB1 -Mut has been shown to promote ACP primary cell proliferation by activating Wnt/β-catenin signaling ( 22 ). On the other hand, reducing the expression of β-catenin can significantly inhibit the proliferation of ACP cells, and β-catenin can promote the expression of Fascin mRNA and Fascin by acting on Fascin genes in the nucleus, thus promoting the migration and invasion ability of ACP cells ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and validation of the critical genes associated with adamantinomatous craniopharyngioma

Fang

Zhou²,

Huang³

et al. 2022

Front. Oncol.

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Adamantinomatous craniopharyngioma (ACP) is an epithelial tumor that arises when Rathke’s pouch remains during embryonic development. The pathogenesis of ACP remains unclear, and treatment options are limited. Here, we reveal the critical genes expressed in ACP and provide a basis for further research and treatment. The raw dataset GSE94349 was downloaded from the GEO database. We selected 24 ACP and 27 matched samples from individuals with no documented tumor complications (control group). Then, we screened for differentially expressed genes (DEGs) to identify key signaling pathways and associated DEGs. A total of 470 DEGs were identified (251 upregulated and 219 downregulated). Hierarchical clustering showed that the DEGs could precisely distinguish the ACP group from the control group (CG). Gene Ontology (GO) enrichment analysis indicated that the upregulated DEGs were mainly involved in cell adhesion, inflammatory responses, and extracellular matrix management. The downregulated DEGs were primarily involved in cell junction and nervous system development. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that the critical pathway was pathways in cancer. In the PPI network, CDH1, SHH, and WNT5A had the highest degrees of interaction and were associated with the formation of ACP. CDH1 was verified as a critical gene by quantitative reverse transcription–polymerase chain reaction (qRT-PCR) in ACP and CG samples. We found that CDH1 may play an important role in the pathways in cancer signaling pathway that regulates ACP development. The CDH1 gene may be a target for future research and treatment of ACP.

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“…In addition, our previous studies also investigated essential transcript factor (TF)–lncRNA pairs based on an integrated algorithm, which provided new insights into the underlying mechanism of ACP development ( 8 ). Currently, the accumulation of beta-catenin caused by CTNNB1 mutations has been recognized as the driver mutations in ACPs ( 9 – 11 ). Studies focusing on the murine ACP model raised a new hypothesis in initiating tumor formation: tumors derived from SOX2− cells transformed by SOX2+ pituitary stem cells expressing beta-catenin in the senescence-associated secretory phenotype (SASP) ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Integrative analyses identify HIF-1α as a potential protective role with immune cell infiltration in adamantinomatous craniopharyngioma

et al. 2022

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Craniopharyngiomas (CPs) are histologically benign tumors located in the sellar–suprasellar region. Although the transcriptome development in recent years have deepened our knowledge to the tumorigenesis process of adamantinomatous craniopharyngioma (ACP), the peritumoral immune infiltration of tumor is still not well understood. In this study, weighted gene coexpression network analysis (WGCNA) was applied to identify different gene modules based on clinical characteristics and gene expression, and then, the protein–protein interaction (PPI) network with the Cytohubba plug-in were performed to screen pivotal genes. In addition, immune cell infiltration (ICI) analysis was used to evaluate the immune microenvironment of ACP patients. In total, 8,568 differential expression genes were identified based on our datasets and two microarray profiles from the public database. The functional enrichment analysis revealed that upregulated genes were mainly enriched in immune-related pathways while downregulated genes were shown in the hormone and transduction of signaling pathways. The WGCNA investigated the most relevant modules, and 1,858 hub genes was detected, from which the PPI network identified 14 pivotal genes, and the Hypoxia-inducible factor 1-alpha (HIF-1α) pathway including four critical genes may be involved in the development of ACP. Moreover, naïve CD4+ and CD8+ T cells were decreased while specific subtypes of T cells were significantly increased in ACP patients according to ICI analysis. Validation by immunofluorescence staining revealed a higher expression of HIF-1α in ACP (ACP vs. control) and adult-subtype (adult vs. children), suggesting a possible state of immune system activation. Notably, children with low HIF-1α scores were related to the hypothalamus involvement and hydrocephalus symptoms. In this study, we successfully identified HIF-1α as a key role in the tumorigenesis and development of ACP through comprehensive integrated analyses and systematically investigated the potential relationship with immune cells in ACP. The results may provide valuable resources for understanding the underlying mechanisms of ACP and strengthen HIF-1α as a potential immunotherapeutic target in clinical application.

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Characterization of novel CTNNB1 mutation in Craniopharyngioma by whole-genome sequencing

Cited by 19 publications

References 67 publications

Molecular biological features of cyst wall of adamantinomatous craniopharyngioma

Molecular biological features of cyst wall of adamantinomatous craniopharyngioma

Bioinformatics analysis and validation of the critical genes associated with adamantinomatous craniopharyngioma

Integrative analyses identify HIF-1α as a potential protective role with immune cell infiltration in adamantinomatous craniopharyngioma

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