Transcriptomic Portraits and Molecular Pathway Activation Features of Adult Spinal Intramedullary Astrocytomas.

Autor: Konovalov N; Burdenko Neurosurgical Center, Moscow, Russia., Timonin S; Burdenko Neurosurgical Center, Moscow, Russia., Asyutin D; Burdenko Neurosurgical Center, Moscow, Russia., Raevskiy M; Omicsway Corp., Walnut, CA, United States.; Moscow Institute of Physics and Technology, Moscow, Russia.; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.; I.M. Sechenov First Moscow State Medical University, Moscow, Russia., Sorokin M; Moscow Institute of Physics and Technology, Moscow, Russia.; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.; I.M. Sechenov First Moscow State Medical University, Moscow, Russia., Buzdin A; Omicsway Corp., Walnut, CA, United States.; Moscow Institute of Physics and Technology, Moscow, Russia.; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.; I.M. Sechenov First Moscow State Medical University, Moscow, Russia.; Oncobox Ltd., Moscow, Russia., Kaprovoy S; Burdenko Neurosurgical Center, Moscow, Russia.
Jazyk: angličtina
Zdroj: Frontiers in oncology [Front Oncol] 2022 Mar 21; Vol. 12, pp. 837570. Date of Electronic Publication: 2022 Mar 21 (Print Publication: 2022).
DOI: 10.3389/fonc.2022.837570
Abstrakt: In this study, we report 31 spinal intramedullary astrocytoma (SIA) RNA sequencing (RNA-seq) profiles for 25 adult patients with documented clinical annotations. To our knowledge, this is the first clinically annotated RNA-seq dataset of spinal astrocytomas derived from the intradural intramedullary compartment. We compared these tumor profiles with the previous healthy central nervous system (CNS) RNA-seq data for spinal cord and brain and identified SIA-specific gene sets and molecular pathways. Our findings suggest a trend for SIA-upregulated pathways governing interactions with the immune cells and downregulated pathways for the neuronal functioning in the context of normal CNS activity. In two patient tumor biosamples, we identified diagnostic KIAA1549-BRAF fusion oncogenes, and we also found 16 new SIA-associated fusion transcripts. In addition, we bioinformatically simulated activities of targeted cancer drugs in SIA samples and predicted that several tyrosine kinase inhibitory drugs and thalidomide analogs could be potentially effective as second-line treatment agents to aid in the prevention of SIA recurrence and progression.
Competing Interests: Author MR was employed by Omicsway Corp and AB was employed by Omicsway Corp. and Oncobox Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Konovalov, Timonin, Asyutin, Raevskiy, Sorokin, Buzdin and Kaprovoy.)
Databáze: MEDLINE