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The high expression of MEOX2 transcription factor is closely associated with poor overall survival in glioma. MEOX2 has recently been described as an interesting prognostic biomarker, especially for lower grade glioma. MEOX2 has never been studied in glioma stem-like cells (GSC), responsible for glioma recurrence. The aim of our study was to investigate the role of MEOX2 in GSC. Loss of function approach using siRNA was used to assess the impact of MEOX2 on GSC viability and stemness phenotype. MEOX2 was localized in the nucleus and its expression was heterogeneous between GSCs. MEOX2 expression depends on the methylation state of its promoter and is strongly associated with IDH mutations. MEOX2 is involved in cell proliferation and viability regulation through ERK/MAPK and PI3K/AKT pathways. MEOX2 loss of function correlated with GSC differentiation and acquisition of neuronal lineage characteristics. Besides, inhibition of MEOX2 is correlated with increased expression of CDH10 and decreased pFAK. In this study, we unraveled, for the first time, MEOX2 contribution to cell viability and proliferation through AKT/ERK pathway and its potential involvement in phenotype and adhesion properties of GSC.

Awake surgery with cognitive monitoring has increasingly been implemented to preserve brain networks and functionality. More recently, not only surgery in the left but also in the right hemisphere, i.c., the parietal lobe, was associated with potential risk for deficits in cognitive functions, such as cognitive flexibility. In this explorative pilot study, we compare cognitive performance more than three months after surgery with baseline measurements and explore the association between cognitive decline and subcortical tracts that may have been severed during surgery in the right hemisphere. Twenty-two patients who underwent surgery for a right parietal low-grade glioma were assessed pre- and postoperatively using the Trail Making Test and the Stroop task to administer set-shifting abilities and inhibition. Volume measurements and lesion-symptom mapping analyses were performed on postoperative MRI scans. Careful interpretation of the results shows a change in TMT performance and not on the Stroop Task when the lateral part of the arcuate fasciculus is damaged, indicating that disconnection of the lateral part of the dorsal stream might be correlated specifically with impaired set-shifting and not with inhibition. More importantly, this study underlines the need for international concertation to allow larger studies to increase power and perform more detailed analyses.

Background: Colorectal cancers (CRC) with brain metastases (BM) are scarcely described. The main objective of this study was to determine the molecular profile of CRC with BM. Methods: We included 82 CRC patients with BM. KRAS , NRAS , BRAF and mismatch repair (MMR) status were investigated on primary tumors ( n = 82) and BM ( n = 38). ALK, ROS1, cMET, HER-2, PD-1, PD-L1, CD3 and CD8 status were evaluated by immunohistochemistry, and when recommended, by fluorescence in situ hybridization. Results: In primary tumors, KRAS , NRAS and BRAF mutations were observed in 56%, 6%, and 6% of cases, respectively. No ROS1 , ALK and cMET rearrangement was detected. Only one tumor presented HER-2 amplification. Molecular profiles were mostly concordant between BM and paired primary tumors, except for 9% of discordances for RAS mutation. CD3, CD8, PD-1 and PD-L1 expressions presented some discordance between primary tumors and BM. In multivariate analysis, multiple BM, lung metastases and PD-L1+ tumor were predictive of poor overall survival. Conclusions: CRCs with BM are associated with high frequency of RAS mutations and significant discordance for RAS mutational status between BM and paired primary tumors. Multiple BM, lung metastases and PD-L1+ have been identified as prognostic factors and can guide therapeutic decisions for CRC patients with BM., Competing Interests: The authors declare no conflict of interest.