Treatment response of CNS high‐grade neuroepithelial tumors with <i>MN1</i> alteration

Baroni, Lorena; Rugilo, Carlos; Lubieniecki, Fabiana; Sampor, Claudia; Freytes, Candela; Nobre, Liana; Hansford, Jordan R.; Malalasekera, Vajiranee S; Zápotocký, Michal; Dodgshun, Andrew; Martínez, Ofelia Cruz; Madrid, Andrés Morales La; Lavarino, Cinzia; Suñol, Mariona; Rutkowski, Stefan; Schüller, Ulrich; Bouffet, Éric; Ramaswamy, Vijay; Alderete, Daniel

doi:10.1002/pbc.28627

Cited by 6 publications

(3 citation statements)

References 11 publications

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“…Moreover, in astroblastoma or neuroepithelial tumors, patients with MN1 rearrangement were reported to have longer survival and better prognosis ( 65 , 68 ). However, some researchers considered no significant superiority in the clinical progression and prognosis of these patients ( 69 ). So far, it is unknown with respect to the relationship between the expression of MN1 at the transcriptome level and the prognosis of glioma.…”

Section: Discussionmentioning

confidence: 99%

Recurrence- and Malignant Progression-Associated Biomarkers in Low-Grade Gliomas and Their Roles in Immunotherapy

Teng

Zhu

et al. 2022

Front. Immunol.

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Despite a generally better prognosis than high-grade glioma (HGG), recurrence and malignant progression are the main causes for the poor prognosis and difficulties in the treatment of low-grade glioma (LGG). It is of great importance to learn about the risk factors and underlying mechanisms of LGG recurrence and progression. In this study, the transcriptome characteristics of four groups, namely, normal brain tissue and recurrent LGG (rLGG), normal brain tissue and secondary glioblastoma (sGBM), primary LGG (pLGG) and rLGG, and pLGG and sGBM, were compared using Chinese Glioma Genome Atlas (CGGA) and Genotype-Tissue Expression Project (GTEx) databases. In this study, 296 downregulated and 396 upregulated differentially expressed genes (DEGs) with high consensus were screened out. Univariate Cox regression analysis of data from The Cancer Genome Atlas (TCGA) yielded 86 prognostically relevant DEGs; a prognostic prediction model based on five key genes (HOXA1, KIF18A, FAM133A, HGF, and MN1) was established using the least absolute shrinkage and selection operator (LASSO) regression dimensionality reduction and multivariate Cox regression analysis. LGG was divided into high- and low-risk groups using this prediction model. Gene Set Enrichment Analysis (GSEA) revealed that signaling pathway differences in the high- and low-risk groups were mainly seen in tumor immune regulation and DNA damage-related cell cycle checkpoints. Furthermore, the infiltration of immune cells in the high- and low-risk groups was analyzed, which indicated a stronger infiltration of immune cells in the high-risk group than that in the low-risk group, suggesting that an immune microenvironment more conducive to tumor growth emerged due to the interaction between tumor and immune cells. The tumor mutational burden and tumor methylation burden in the high- and low-risk groups were also analyzed, which indicated higher gene mutation burden and lower DNA methylation level in the high-risk group, suggesting that with the accumulation of genomic mutations and epigenetic changes, tumor cells continued to evolve and led to the progression of LGG to HGG. Finally, the value of potential therapeutic targets for the five key genes was analyzed, and findings demonstrated that KIF18A was the gene most likely to be a potential therapeutic target. In conclusion, the prediction model based on these five key genes can better identify the high- and low-risk groups of LGG and lay a solid foundation for evaluating the risk of LGG recurrence and malignant progression.

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Section: Discussionmentioning

confidence: 99%

Recurrence- and Malignant Progression-Associated Biomarkers in Low-Grade Gliomas and Their Roles in Immunotherapy

Teng

Zhu

et al. 2022

Front. Immunol.

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“…The determinants of this vast difference in outcomes despite the unifying molecular diagnosis remain unknown and likely include clinical features, tumor genomics and treatment modalities. Table 2 also highlights a discrepancy between PFS and OS as many patients experience short PFS yet prolonged OS with some experiencing late recurrences ( 9 , 11 ). Sturm and colleagues reported that of the eight patients diagnosed with HGNET-MN1 in their study, 100% experienced an overall survival (OS) beyond 8 years, but only two had a progression-free survival (PFS) that extended beyond 6 years ( 2 ).…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous clinicopathological findings and patient-reported outcomes in adults with MN1-altered CNS tumors: A case report and systematic literature review

et al. 2023

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The uncommon MN1-altered primary central nervous system (CNS) tumors were recently added to the World Health Organization 2021 classification under the name Astroblastoma, MN1-altered. Another term used to describe them, “High-grade neuroepithelial tumor with MN1 alteration” (HGNET-MN1), makes reference to their distinct epigenetic profile but is currently not a recommended name. Thought to occur most commonly in children and predominantly in females, MN1-altered CNS tumors are associated with typical but not pathognomonic histological patterns and are characterized by a distinct DNA methylation profile and recurrent fusions implicating the MN1 (meningioma 1) gene. Diagnosis based on histological features alone is challenging: most cases with morphological features of astroblastoma (but not all) show these molecular features, whereas not all tumors with MN1 fusions show astroblastoma morphology. There is large variability in reported outcomes and detailed clinical and therapeutic information is frequently missing. Some patients experience multiple recurrences despite multimodality treatment, whereas others experience no recurrence after surgical resection alone, suggesting large clinical and biological heterogeneity despite unifying epigenetic features and recurrent fusions. In this report, we present the demographics, tumor characteristics, treatment, and outcome (including patient-reported outcomes) of three adults with MN1-altered primary CNS tumors diagnosed via genome-wide DNA methylation and RNA sequencing. All three patients were females and two of them were diagnosed as young adults. By reporting our neuropathological and clinical findings and comparing them with previously published cases we provide insight into the clinical heterogeneity of this tumor. Additionally, we propose a model for prospective, comprehensive, and systematic collection of clinical data in addition to neuropathological data, including standardized patient-reported outcomes.

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“…Suggested molecular work-up of STE in AYA patients involves testing for ZFTA fusions, which can be identified via fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), next generation sequencing (NGS), or nanoString ( 45 ). In the AYA population, if a ZFTA fusion is not present then alternate diagnoses such as GBM with ependymal differentiation ( 46 ), or MN1-fused or BCOR-fused neuroepithelial tumors, should be considered ( 47 , 48 ).…”

Section: Ependymomamentioning

confidence: 99%

Molecular testing for adolescent and young adult central nervous system tumors: A Canadian guideline

et al. 2022

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The 2021 World Health Organization (WHO) classification of CNS tumors incorporates molecular signatures with histology and has highlighted differences across pediatric vs adult-type CNS tumors. However, adolescent and young adults (AYA; aged 15–39), can suffer from tumors across this spectrum and is a recognized orphan population that requires multidisciplinary, specialized care, and often through a transition phase. To advocate for a uniform testing strategy in AYAs, pediatric and adult specialists from neuro-oncology, radiation oncology, neuropathology, and neurosurgery helped develop this review and testing framework through the Canadian AYA Neuro-Oncology Consortium. We propose a comprehensive approach to molecular testing in this unique population, based on the recent tumor classification and within the clinical framework of the provincial health care systems in Canada.Contributions to the fieldWhile there are guidelines for testing in adult and pediatric CNS tumor populations, there is no consensus testing for AYA patients whose care occur in both pediatric and adult hospitals. Our review of the literature and guideline adopts a resource-effective and clinically-oriented approach to improve diagnosis and prognostication of brain tumors in the AYA population, as part of a nation-wide initiative to improve care for AYA patients.

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Treatment response of CNS high‐grade neuroepithelial tumors with MN1 alteration

Cited by 6 publications

References 11 publications

Recurrence- and Malignant Progression-Associated Biomarkers in Low-Grade Gliomas and Their Roles in Immunotherapy

Recurrence- and Malignant Progression-Associated Biomarkers in Low-Grade Gliomas and Their Roles in Immunotherapy

Heterogeneous clinicopathological findings and patient-reported outcomes in adults with MN1-altered CNS tumors: A case report and systematic literature review

Molecular testing for adolescent and young adult central nervous system tumors: A Canadian guideline

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