Decoding the Role of DVL1 in Intracranial Meningioma

Scientific paper - Original scientific paper

• Author: Anja Bukovac
• Author: Katarina Dragičević
• Author: Anja Kafka
• Author: Darko Orešković
• Author: Sanja Cesarec-Augustinović
• Author: Nives Pećina-Šlaus
• Author's institution: University of Zagreb; School of Medicine; (Croatian Institiute for Brain Research)
• Author's institution: University of Zagreb; School of Medicine; (Department of Medical Biology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences

Abstract (english)

In the search for molecular candidates for targeted meningioma therapies, increasing attention has been paid to the role of signaling pathways in the development and progression of intracranial meningiomas. Although it is well known that the Wnt signaling pathway is involved in meningioma progression, the role of its central mediator, DVL1, is still unclear. In order to investigate the influence of DVL1 gene alterations on the progression of human intracranial meningioma, we focused on its central PDZ domain, which is responsible for DVL interaction with the Fzd receptor and the phosphorylation of DVL mediated through the casein kinases CK1 and CK2. A genetic analysis of genomic instability revealed the existence of microsatellite instability in 9.09% and the loss of heterozygosity in 6.06% of the samples. The sequencing of the PDZ gene region showed repetitive deletions of two bases located in intron 7 and exon 8, and a duplication in intron 8 in most samples, with different outcomes on the biological function of the DVL1 protein. Immunohistochemistry revealed that the nuclear expression of DVL1 was significantly correlated with a higher expression of active β-catenin (p = 0.029) and a higher meningioma grade (p = 0.030), which leads to the conclusion that it could be used as biomarker for meningioma progression and the activation of the Wnt signaling pathway.

• Keywords (english): Adult; Aged; Aged, 80 and over; Biomarkers, Tumor / genetics; Biomarkers, Tumor / metabolism; Dishevelled Proteins / genetics*; Dishevelled Proteins / metabolism; Female; Humans; Male; Meningeal Neoplasms / genetics; Meningeal Neoplasms / metabolism; Meningeal Neoplasms / pathology; Meningioma / genetics*; Meningioma / metabolism; Meningioma / pathology; Microsatellite Instability; Middle Aged; Mutation; PDZ Domains; Prognosis; Young Adult; beta Catenin / genetics; beta Catenin / metabolism
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: International Journal of Molecular Sciences
• Numbering: vol. 22, no. 21, 11996
• e-ISSN: 1422-0067
• DOI: https://doi.org/10.3390/ijms222111996
• URN:NBN: urn:nbn:hr:105:542236
• Publication: 2021-11-05
• Document URL: https://www.mdpi.com/1422-0067/22/21/11996
• Type of resource: Text
• Access conditions: Open access
• Created on: 2022-03-11 09:38:14