Kondaboina, S.; Parrish, O.; Parada, C. A.; Ferreira Jr, M. Somatic Landscape of Intracranial Epidermoid Cysts Reveals Immune-Associated Mechanistic and Potential Actionable Targets. Preprints2024, 2024090462. https://doi.org/10.20944/preprints202409.0462.v1
APA Style
Kondaboina, S., Parrish, O., Parada, C. A., & Ferreira Jr, M. (2024). Somatic Landscape of Intracranial Epidermoid Cysts Reveals Immune-Associated Mechanistic and Potential Actionable Targets. Preprints. https://doi.org/10.20944/preprints202409.0462.v1
Chicago/Turabian Style
Kondaboina, S., Carolina Angelica Parada and Manuel Ferreira Jr. 2024 "Somatic Landscape of Intracranial Epidermoid Cysts Reveals Immune-Associated Mechanistic and Potential Actionable Targets" Preprints. https://doi.org/10.20944/preprints202409.0462.v1
Abstract
Background/Objectives: Intracranial Epidermoid Cysts (IECs) are extremely rare intracranial tumors. The primary treatment is surgery; however, cyst adherence results in difficult removal; subtotal resection yields high recurrence rates. The mechanisms of IECs remain unknown, consequently, advances in treatment have fallen short. Tumor genetic profiling has rendered targets for drug development and for which FDA-approved options exist, reshaping cancer treatment. The genetics of IECs has not been explored. We applied Whole Exome Sequencing (WES) in IECs to gain insights into the mechanisms of oncogenesis and identify actionable targets. Methods: We performed WES in tumor tissue and matching blood, when available. Read processing, quality control and somatic variant calling followed GATK best practices. Read alignments were also used for somatic copy-number inference. Data analyses and visualizations were conducted in R. Results: Top altered genes were associated with immune system and microenvironment, suggesting an immune evasion mechanism. Recurrent and deleterious NOTCH2 and USP8 alterations were identified in 50% and 30% of the cohort, respectively. Frequent amplifications in deubiquitinases and beta-defensins, strengthened the involvement of an immune mechanism for oncogenic transformation. Drug-gene interactions highlighted NOTCH2 as clinically relevant for which FDA-approved treatments exists. Conclusions: Top altered genes may have a role in shaping an epidermoid cyst-permissive tumor microenvironment and modulating tumor immune evasion. USP8 and NOTCH2 may be clinically relevant drivers of IECs. NOTCH2 may be an interesting candidate for drug repurposing.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
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