| Full text | |
| Author(s): Show less - |
Pereira, Benedito Jamilson Araujo
;
Lerario, Antonio Marcondes
;
Sola, Paula Rodrigues
;
Laurentino, Talita de Sousa
;
Mohan, Dipika R.
;
Almeida, Antonio Nogueira de
;
de Aguiar, Paulo Henrique Pires
;
Paiva, Wellingson da Silva
;
Wakamatsu, Alda
;
Teixeira, Manoel Jacobsen
;
Oba-Shinjo, Sueli Mieko
;
Marie, Suely Kazue Nagahashi
Total Authors: 12
|
| Document type: | Journal article |
| Source: | JOURNAL OF NEUROSURGERY; v. 138, n. 3, p. 14-pg., 2022-03-01. |
| Abstract | |
OBJECTIVE The authors searched for genetic and transcriptional signatures associated with tumor progression and recurrence in their cohort of patients with meningiomas, combining the analysis of targeted exome, NF2-LOH, transcrip-tome, and protein expressions. METHODS The authors included 91 patients who underwent resection of intracranial meningioma at their institution between June 2000 and November 2007. The search of somatic mutations was performed by Next Generation Sequenc-ing through a customized panel and multiplex ligation-dependent probe amplification for NF2 loss of heterozygosity. The transcriptomic profile was analyzed by QuantSeq 3 ' mRNA-Seq. The differentially expressed genes of interest were validated at the protein level analysis by immunohistochemistry.RESULTS The transcriptomic analysis identified an upregulated set of genes related to metabolism and cell cycle and downregulated genes related to immune response and extracellular matrix remodeling in grade 2 (atypical) meningio-mas, with a significant difference in recurrent compared with nonrecurrent cases. EZH2 nuclear positivity associated with grade 2, particularly with recurrent tumors and EZH2 gene expression level, correlated positively with the expres-sion of genes related to cell cycle and negatively to genes related to immune response and regulation of cell motility. CONCLUSIONS The authors identified modules of dysregulated genes in grade 2 meningiomas related to the activation of oxidative metabolism, cell division, cell motility due to extracellular remodeling, and immune evasion that were predic-tive of survival and exhibited significant correlations with EZH2 expression. (AU) | |
| FAPESP's process: | 14/50137-5 - Caracterização molecular de doenças monogênicas do desenvolvimento por sequenciamento em larga escala |
| Grantee: | Berenice Bilharinho de Mendonça |
| Support Opportunities: | Multi-user Equipment Program |
| FAPESP's process: | 20/02988-7 - Decoding the impact of microenvironment and signaling pathways in health and disease in brain, adrenal gland and kidney |
| Grantee: | Suely Kazue Nagahashi Marie |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 01/12898-4 - Genoma clínico |
| Grantee: | Suely Kazue Nagahashi Marie |
| Support Opportunities: | Genome Research Grants |
| FAPESP's process: | 13/02162-8 - Molecular pathogenesis and characterization of monogenic developmental diseases: a route to translational medicine |
| Grantee: | Berenice Bilharinho de Mendonça |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 04/12133-6 - Search for molecular markers related to the diagnosis and prognosis of tumors of the central nervous system |
| Grantee: | Suely Kazue Nagahashi Marie |
| Support Opportunities: | Research Projects - Thematic Grants |