Mb-87integrated Genomics Reveals Novel Subtypes of Medulloblastoma Subgroups

Cavalli, Florence M.G.; Remke, Marc; Reimand, Jüri; Rampášek, Ladislav; Goldenberg, Anna; Taylor, Michael D.; Ramaswamy, Vijay

doi:10.1093/neuonc/now076.83

Cited by 13 publications

(50 citation statements)

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“…37 Building on the classification of medulloblastoma into subgroups, recent integrated analysis of DNA methylation, gene expression, copy number alterations, and clinical data has suggested the existence of subtypes of medulloblastoma within each subgroup. 7 Using gene expression and methylation array data, Cavalli et al suggested the existence of two WNT subtypes: WNTα and WNTβ. 7 The WNTα subtype primarily occurred in children and 98% of these cases had monosomy 6, whereas the WNTβ subtype occurred in older children and adults and infrequently (29%) had monosomy 6.…”

Section: Wntmentioning

confidence: 99%

“…7 Using gene expression and methylation array data, Cavalli et al suggested the existence of two WNT subtypes: WNTα and WNTβ. 7 The WNTα subtype primarily occurred in children and 98% of these cases had monosomy 6, whereas the WNTβ subtype occurred in older children and adults and infrequently (29%) had monosomy 6. 7…”

Section: Wntmentioning

confidence: 99%

“…46 Outcomes in this subgroup vary according to clinical (age and metastatic status) and molecular (MYCN amplification and TP53 mutation status) characteristics. 7,50 SHH tumors are thought to arise from granule cell precursors of the external granule layer. 17,67 The majority of these tumors contain germline or somatic mutations or copy number alterations in the SHH signaling pathway, leading to constitutively activated SHH signaling, driving tumor development and progression.…”

Section: Shhmentioning

confidence: 99%

“…39 TERT promoter mutations are also found in 39% of SHH tumors (including nearly all adult SHH cases). 7,36 Frequently occurring cytogenetic events in this group include loss of chromosome 9q (causing loss of heterozygosity of PTCH1) and 10q (loss of SUFU). 36 Up to four different SHH subtypes have been de-scribed.…”

Section: Shhmentioning

confidence: 99%

“…31 The expanding wealth of molecular data from patient samples has started to allow further refinement of these subgroups, with numerous subtypes of medulloblastoma being recognized. 7,36,59 In this review, our current understanding of this fascinating disease will be reviewed, including the molecular underpinnings of this disease, risk stratification, treatment protocols, and the landscape of current clinical trials. Subsequently, key areas of future inquiry in basic science and clinical trials will be discussed.…”

mentioning

confidence: 99%

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Medulloblastoma in the age of molecular subgroups: a review

Juraschka

Taylor

2019

Journal of Neurosurgery: Pediatrics

169

167

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Medulloblastoma is the most common pediatric malignant brain tumor. Advances in molecular profiling have uncovered significant heterogeneity among medulloblastomas and led to the identification of four distinct subgroups (wingless [WNT], sonic hedgehog [SHH], group 3, and group 4) that represent distinct disease entities in both underlying biology and clinical characteristics. The rapidly expanding repertoire of tools to study developmental and cancer biology is providing a wealth of knowledge about these embryonal tumors and is continuously refining the understanding of this complex cancer. In this review, the history of discovery in medulloblastoma is discussed, setting a foundation to outline the current state of understanding of the molecular underpinnings of this disease, with a focus on genomic events that define the aforementioned subgroups and evolving areas of focus, such as the cell of origin of medulloblastoma and medulloblastoma subtypes. With these recent discoveries in mind, the current state of medulloblastoma treatment and clinical trials is reviewed, including a novel risk stratification system that accounts for the molecular biomarkers of patients with a high risk for refractory disease. Lastly, critical areas of focus for future basic science and clinical research on this disease are discussed, such as the complexities of medulloblastoma metastases and recurrence as well as the priorities and strategies to implement in future clinical trials.

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Section: Wntmentioning

confidence: 99%

Section: Wntmentioning

confidence: 99%

Section: Shhmentioning

confidence: 99%

Section: Shhmentioning

confidence: 99%

mentioning

confidence: 99%

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Medulloblastoma in the age of molecular subgroups: a review

Juraschka

Taylor

2019

Journal of Neurosurgery: Pediatrics

169

167

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Beijing Children’s Hospital guidelines on the design and conduction of the first standardized database for medulloblastoma

Yang

Huang

et al. 2023

Metab Brain Dis

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Medulloblastoma (MB) is one of the most common malignant childhood brain tumors (WHO grade IV).Its high degree of malignancy leads to an unsatisfactory prognosis, requiring more precise and personalized treatment in the near future. Multi-omics and arti cial intelligence have been playing a signi cant role in precise medical research, but their implementation needs a large amount of clinical information and biomaterials. For these reasons, it is urgent for current MB researchers to establish a large sample-size database of MB that contains complete clinical data and su cient biomaterials such as blood, cerebrospinal uid (CSF), cancer tissue, and urine. Unfortunately, there are few biobanks of pediatric central nervous system (CNS) tumors throughout the world for limited specimens, scarce funds, different standards collecting methods and et cl. Even though, China falls behind western countries in this area. The present research set up a standard work ow to construct the Beijing Children's Hospital Medulloblastoma (BCH-MB) biobank. Clinical data from children with MB and for collecting and storing biomaterials, along with regular follow-up has been collected and recorded in this database. In the future, the BCH-MB biobank could make it possible to validate the promising biomarkers already identi ed, discover unrevealed MB biomarkers, develop novel therapies, and establish personalized prognostic models for children with MB upon the support of its su cient data and biomaterials, laying the foundation for individualized therapies of children with MB.

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Immunohistochemical Surrogates for Molecular Stratification in Medulloblastoma

Chinnam¹,

Saraswati²,

Jogunoori³

et al. 2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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Background: The WHO classification of central nervous system neoplasms (2016) recognized 4 histologic variants and genetically defined molecular subgroups within medulloblastoma (MB). Further, in the 2021 classification, new subtypes have been provisionally added within the existing subgroups reflecting the biological diversity. YAP1, GAB1, and β-catenin were conventionally accepted as surrogate markers to identify these genetic subgroups. Objectives: We aimed to stratify MB into molecular subgroups using 3 immunohistochemical markers. TP53 mutation was also assessed in Wingless (WNT), and Sonic Hedgehog (SHH) subgroups. Demographic profiles, imaging details, and survival outcomes were compared within these molecular subgroups. Patients and methods: Our cohort included 164 MB cases diagnosed over the last 10 years. The histologic variants were identified on histology, and tumors were molecularly stratified using YAP1, GAB1, and β-catenin. Further, TP53 mutation was assessed using immunohistochemical in WNT and SHH subgroups. The clinical details and survival outcomes were retrieved from the records, and the mentioned correlates were evaluated statistically. Results: The age ranged from 1 to 52 years with M:F ratio of 2:1. Group 3/group 4 constituted the majority (48.4%), followed by SHH (45.9%) and WNT subgroups (5.7%). Desmoplastic/nodular and MB with extensive nodularity had the best survival, whereas large cell/anaplastic had the worst. The follow-up period ranged from 1 to 129 months. The best outcome was observed for the WNT subgroup, followed by the SHH subgroup; group 3/group 4 had the worst. Among the SHH subgroup, TP53 mutant tumors had a significantly poorer outcome compared with SHH-TP53 wildtype. Conclusions: Molecular stratification significantly contributes to prognostication, and a panel of 3 antibodies is helpful in stratifying MB into its subgroups in centers where access to advanced molecular testing is limited. Our study reinforces the efficacy of incorporating this cost-effective, minimal panel into routine practice for stratification. Further, we propose a 3-risk stratification grouping, incorporating morphology and molecular markers.

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Mb-87integrated Genomics Reveals Novel Subtypes of Medulloblastoma Subgroups

Cited by 13 publications

References 0 publications

Medulloblastoma in the age of molecular subgroups: a review

Medulloblastoma in the age of molecular subgroups: a review

Beijing Children’s Hospital guidelines on the design and conduction of the first standardized database for medulloblastoma

Immunohistochemical Surrogates for Molecular Stratification in Medulloblastoma

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