Group-specific cellular metabolism in Medulloblastoma

Funke, Viktoria L. E.; Walter, Carolin; Melcher, Viktoria; Wei, Lanying; Sandmann, Sarah; Hotfilder, Marc; Varghese, Julian; Jäger, Natalie; Kool, Marcel; Jones, David T. W.; Pfister, Stefan M.; Milde, Till; Mynarek, Martin; Rutkowski, Stefan; Seggewiss, Jochen; Jeising, Daniela; de Faria, Flavia W.; Marquardt, Thorsten; Albert, Thomas K.; Schüller, Ulrich; Kerl, Kornelius

doi:10.1186/s12967-023-04211-6

Cited by 3 publications

(2 citation statements)

References 56 publications

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“…In this study, we generated tumor specific co-expression profiles for pediatric MB patients and delineated that the Group 4 subtype was highly correlated with the ribosome pathway. Moreover, we observed significantly elevated GSVA RB scores in the other three molecular subtypes, similar with previous studies [21][22][23]24 , pinpointing the RB signature as a potential genetic marker for subtype classifications.…”

Section: Discussionsupporting

confidence: 91%

In-depth Inference of Transcriptional Regulatory Networks Identifies NPM1 as a Druggable Master Regulator in Medulloblastoma

Lin,

Dong,

Chen

et al. 2023

Preprint

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Medulloblastoma (MB) is a highly malignant embryonic brain tumor with distinct cytogenetic heterogeneity in children. Despite elucidating divergent regulatory underpinnings in MB molecular subtypes, the hidden oncogenic signaling drivers with minimal differential expression remain obscure. Here, we leveraged two bulk RNA-seq datasets involving 1055 patients to construct pediatric MB specific co-expression profiles and regulatory networks, unveiling unique attributes of the ribosome pathway in different molecular subtypes. NPM1, a pivotal ribosome regulator, was pinpointed as a promising targetable driver for MB by integrating differentially expressed candidates and reported drug targets. To assess the role of NPM1 in MB progression, we employed NETBID2 gene activity algorithm, Kaplan–Meier survival curves, single-cell RNA-seq (scRNA-seq) analysis, and functional validations in MB cell lines. Our findings highlighted substantial correlations between the activity values of NPM1 and the prognosis of MB patients, eclipsing the significance of its expression levels. Furthermore, NPM1 was extensively and highly expressed in early SOX2 positive neural stem cells and tumor cells. Deficiency of NPM1 impeded MB cell growth, triggered apoptosis and led to a reduction of c-Myc levels. Our findings provide new approaches for exploring underlying pathways and underscore the clinical transformation value of NPM1 as a master regulator for MB.

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Section: Discussionsupporting

confidence: 91%

In-depth Inference of Transcriptional Regulatory Networks Identifies NPM1 as a Druggable Master Regulator in Medulloblastoma

Lin,

Dong,

Chen

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In particular, high-risk metabolic clusters comprise G3/G4 methylation subgroup, MYC-amplified. MYC amplification displayed upregulation of genes related to nucleotide metabolism and oxidative phosphorylation, making them a potential therapeutic target ( Gwynne et al, 2022 ; Funke et al, 2023 ).…”

Section: Embryonal Tumorsmentioning

confidence: 99%

Pediatric CNS tumors and 2021 WHO classification: what do oncologists need from pathologists?

d’Amati,

Bargiacchi,

Rossi

et al. 2024

Front. Mol. Neurosci.

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The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, established new approaches to both CNS tumor nomenclature and grading, emphasizing the importance of integrated diagnoses and layered reports. This edition increased the role of molecular diagnostics in CNS tumor classification while still relying on other established approaches such as histology and immunohistochemistry. Moreover, it introduced new tumor types and subtypes based on novel diagnostic technologies such as DNA methylome profiling. Over the past decade, molecular techniques identified numerous key genetic alterations in CSN tumors, with important implications regarding the understanding of pathogenesis but also for prognosis and the development and application of effective molecularly targeted therapies. This review summarizes the major changes in the 2021 fifth edition classification of pediatric CNS tumors, highlighting for each entity the molecular alterations and other information that are relevant for diagnostic, prognostic, or therapeutic purposes and that patients’ and oncologists’ need from a pathology report.

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Metabolomic profiling of childhood medulloblastoma: contributions and relevance to diagnosis and molecular subtyping

Huang,

Lu,

Sun

et al. 2024

J Cancer Res Clin Oncol

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The incidence of brain tumors among children is second only to acute lymphoblastic leukemia, but the mortality rate of brain tumors has exceeded that of leukemia, making it the most common cause of death among children. Medulloblastoma (MB) is the most common type of brain tumor among children. Malignant brain tumors have strong invasion and metastasis capabilities, can spread through cerebrospinal fluid, and have a high mortality rate. In 2010, the World Health Organization first divided MB into four molecular subtypes based on molecular markers: WNT, Sonic hedgehog (SHH), Group 3, and Group 4. MB is a highly heterogeneous tumor. Different molecular subtypes of MB have significantly different clinical, pathological, and molecular characteristics. The prognosis of MB varies significantly among patients with different subtypes of this cancer. Thus, it is needed to study new diagnostic and therapeutic strategies. Metabolomics is an advanced analytical technology that uses various spectroscopic, electrochemical, and data analysis technologies to study and analyze the body’s metabolites. By detecting changes in metabolite types and quantities in different types of samples, it can sensitively discover the physiological and pathological changes in the body. It has great potential for clinical application and personalized medicine. It is promising and can help develop personalized treatment strategies based on the metabolic profiles of individuals. It can unravel the unique metabolic profiles of MB, which may revolutionize our understanding of the disease and improve patients’ outcomes.

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Group-specific cellular metabolism in Medulloblastoma

Cited by 3 publications

References 56 publications

In-depth Inference of Transcriptional Regulatory Networks Identifies NPM1 as a Druggable Master Regulator in Medulloblastoma

In-depth Inference of Transcriptional Regulatory Networks Identifies NPM1 as a Druggable Master Regulator in Medulloblastoma

Pediatric CNS tumors and 2021 WHO classification: what do oncologists need from pathologists?

Metabolomic profiling of childhood medulloblastoma: contributions and relevance to diagnosis and molecular subtyping

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