Risk Factors for Survival in Patients With Medulloblastoma: A Systematic Review and Meta-Analysis

Liu, Yu; Xiao, Bo; Li, Sen; Liu, Jiangang

doi:10.3389/fonc.2022.827054

Cited by 13 publications

(9 citation statements)

References 58 publications

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“…The malignant childhood tumor medulloblastoma is heterogeneous 3 , especially in the Groups 3 and 4 . This heterogeneity makes effective treatment of these tumors difficult and contributes to overall low survival rates 4 . Advanced DNA methylation profiling has classified Group 3/4 tumors into 8 distinct molecular subgroups 5 .…”

Section: Mainmentioning

confidence: 99%

Medulloblastoma oncogene aberrations are not involved in tumor initiation, but essential for disease progression and therapy resistance

Okonechnikov,

Joshi,

Körber

et al. 2024

Preprint

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Despite recent advances in understanding disease biology, treatment of Group 3/4 medulloblastoma remains a therapeutic challenge in pediatric neuro-oncology. Bulk-omics approaches have identified considerable intertumoral heterogeneity in Group 3/4 medulloblastoma, including the presence of clear single-gene oncogenic drivers in only a subset of cases, whereas in the majority of cases, large-scale copy-number aberrations prevail. However, intratumoral heterogeneity, the role of oncogene aberrations, and broad CNVs in tumor evolution and treatment resistance remain poorly understood. To dissect this interplay, we used single-cell technologies (snRNA-seq, snATAC-seq, spatial transcriptomics) on a cohort of Group 3/4 medulloblastoma with known alterations in the oncogenes MYC, MYCN, and PRDM6. We show that large-scale chromosomal aberrations are early tumor initiating events, while the single-gene oncogenic events arise late and are typically sub-clonal, but MYC can become clonal upon disease progression to drive further tumor development and therapy resistance. We identify that the subclones are mostly interspersed across tumor tissue using spatial transcriptomics, but clear segregation is also present. Using a population genetics model, we estimate medulloblastoma initiation in the cerebellar unipolar brush cell-lineage starting from the first gestational trimester. Our findings demonstrate how single-cell technologies can be applied for early detection and diagnosis of this fatal disease.

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Section: Mainmentioning

confidence: 99%

Medulloblastoma oncogene aberrations are not involved in tumor initiation, but essential for disease progression and therapy resistance

Okonechnikov,

Joshi,

Körber

et al. 2024

Preprint

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“…The wingless/integral (WNT) subgroup has a good prognosis, the sonic hedgehog (SHH) subgroup and group 4 have an intermediate prognosis, while subgroup 3 has a poor prognosis [17,18]. A recent meta-analysis suggests that the histologic characteristics of MB, molecular subgroups of MB, GTR, and radiotherapy are the most important prognostic factors associated with survival in patients with MB [19]. Epigenetic modifications, including DNA methylation patterns and chromatin remodeling, have emerged as critical determinants of MB prognosis.…”

Section: Prognosis Of Mbmentioning

confidence: 99%

Medulloblastoma diagnosis and treatment

Zafari,

Azarhomayoun

2024

Medulloblastoma - Therapeutic Outcomes and Future Clinical Trials [Working Title]

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Medulloblastoma is the most common malignant brain tumor in children. About 16–20% of all primary brain tumors in children are medulloblastoma, and it accounts for about 40% of all cerebellar tumors in childhood. The incidence of medulloblastoma peaked in those aged 9 years and younger. Some of the most common clinical symptoms of medulloblastoma are headache, vomiting, vertigo, and ataxia. Additional manifestations that may occur include lethargy, irritability, motor or cranial nerve impairment, gaze-palsy, sphincter disorders, and back pain in those with spinal metastases. Imaging tests can help determine the location and size of the brain tumor. A computerized tomography (CT) scan or magnetic resonance imaging (MRI) may be done immediately. It is uncommon to do a biopsy, but it may be recommended if the imaging studies are not typical of medulloblastoma. The treatment for medulloblastoma depends on several factors, including clinical conditions of the patient and the size and location of the tumor. Treatment methods for medulloblastoma usually include surgery followed by radiotherapy, chemotherapy, or both. Treatment for medulloblastoma focuses on removing as much of the tumor as safely possible and relieving intracranial pressure. This three-part approach, surgery, radiotherapy, and chemotherapy, can increase the survival of patients by up to 75%.

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“…In this case, the five-year post-diagnosis overall survival (OS) is 85%. If at least one of these criteria is unmet, the patient is considered high-risk, and the 5-year OS drops to 60% (7). Despite the recent identification of four core molecular subgroups (SHH, WNT, group 3, and group 4), clinical stratification of the patients still mainly relies on the clinical features described above.…”

Section: Introductionmentioning

confidence: 99%

“…If at least one of these criteria is unmet, the patient is considered high-risk, and the 5-year OS drops to 60% (7).…”

Section: Introductionmentioning

confidence: 99%

Integrin-αVβ3 is a fundamental factor in medulloblastoma tumorigenicity and radioresistance: A new game for an old player

Echavidre

Durivault

Gotorbe

et al. 2023

Preprint

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Medulloblastoma (MB) is the most frequent solid tumor in children, localized in the brain posterior fossa. Its standard of care comprises maximal resection surgery followed by craniospinal irradiation and chemotherapy. Despite a long-term survival rate of 70%, wide disparities among patients have been observed. Relevant targets for naive and recurrent MB are urgently needed. Primary and recurrent MBs are characterized by aggressive invasion into surrounding brain tissue, active angiogenesis, and radioresistance. Integrin-alpha v beta 3 was a major driver of these features in glioblastoma. Nevertheless, such observations have not yet been reported in MB. Integrin alpha v beta 3 was found to be expressed in a subset of MB patients. We investigated the role of integrin-alpha v beta 3 using MB-derived cell lines with beta 3 -subunit depletion or overexpression both in vitro and in vivo. Radioresistant MB cell lines were generated and showed increased integrin-alpha v beta 3 expression, which correlated with increased susceptibility to pharmacological integrin-alpha v beta 3 inhibition with cilengitide, a competitive ligand mimetic. Finally, we conducted single-photon emission computed tomography (SPECT)/magnetic resonance imaging (MRI) studies on orthotopic models using a radiolabeled integrin-alpha v beta 3 ligand (99mTc-RAFT-RGD). This approach offers the prospect of a novel predictive imaging modality in MB. Altogether, our data pave the way for SPECT/MRI-based selection of a subpopulation of MB patients eligible for integrin-alpha v beta 3-directed therapies.

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Risk Factors for Survival in Patients With Medulloblastoma: A Systematic Review and Meta-Analysis

Cited by 13 publications

References 58 publications

Medulloblastoma oncogene aberrations are not involved in tumor initiation, but essential for disease progression and therapy resistance

Medulloblastoma oncogene aberrations are not involved in tumor initiation, but essential for disease progression and therapy resistance

Medulloblastoma diagnosis and treatment

Integrin-αVβ3 is a fundamental factor in medulloblastoma tumorigenicity and radioresistance: A new game for an old player

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