Medulloblastoma, WNT-activated/SHH-activated: clinical impact of molecular analysis and histogenetic evaluation

Cambruzzi, Eduardo

doi:10.1007/s00381-018-3765-2

Cited by 20 publications

(14 citation statements)

References 51 publications

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“…Strongly positive immune-expression of GAB1 was observed in non-desmoplastic SHH-activated medulloblastomas. 21,22 In fact, in the present case, the tumor cells from the third surgery showed diffuse and intense positivity for GAB1 compared with those from the first and second surgeries immunohistochemically, but they did not show nuclear positivity for beta-catenin. Regarding p53, tumor cells from the third specimens showed more scattered positivity compared to those of the earlier specimens, but not diffuse positivity.…”

Section: Discussioncontrasting

confidence: 48%

“…It is tyrosine‐phosphorylated on stimulation of receptors by many growth factors and interacts with multiple signaling molecules. Strongly positive immune‐expression of GAB1 was observed in non‐desmoplastic SHH‐activated medulloblastomas . In fact, in the present case, the tumor cells from the third surgery showed diffuse and intense positivity for GAB1 compared with those from the first and second surgeries immunohistochemically, but they did not show nuclear positivity for beta‐catenin.…”

Section: Discussioncontrasting

confidence: 46%

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Malignant progression of an extraventricular neurocytoma arising from the VIIIth cranial nerve: A case report and literature review

et al. 2018

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A rare case of extraventricular neurocytoma (EVN) arising from the VIIIth cranial nerve in a 34‐year‐old woman is reported. The patient had a 20‐year history of hearing loss and facial palsy. Computed tomography showed a 3‐cm enhancing lesion in the left cerebellopontine angle (CPA). At operation, the tumor was seen to originate from the cochlear and vestibular nerves. The tumor was subtotally resected. Histologically, the tumor consisted of uniform cells with oval to round nuclei and scant cytoplasm. Immunohistochemically, the tumor cells were positive for synaptophysin, but negative for glial fibrillary acid protein and S‐100 protein. The Ki‐67 labeling index was 0%. Twelve years after the operation, magnetic resonance imaging (MRI) showed tumor recurrence at the left CPA. The tumor was subtotally resected, and radiation therapy was given. Histologically, the tumor consisted of round cells with mild atypia and one mitosis/20 high‐power fields (HPF). Immunohistochemically, tumor cells showed the same findings as the first operation sample, except for the Ki‐67 labeling index (3%). Twelve years after the second operation, MRI showed a second tumor recurrence at the left CPA and surroundings of the brain stem. The tumor was subtotally resected. Histologically, the tumor consisted of anaplastic short spindle cells and five mitoses/10 HPF. The immunohistochemical findings were almost the same as the earlier operation samples. However, the Ki‐67 labeling index was 20%. In addition, tumor cells from the third specimen were more strongly and more diffusely positive for GAB1 (growth factor receptor‐bound protein 2‐associated binding protein 1) compared to those of the earlier specimens. Electron microscopy showed the presence of numerous cell processes with a dense core and clear vesicles and microtubules. GAB1 immunostaining also indicated that malignant progression might be associated with the sonic hedgehog signaling pathways. To the best of our knowledge, this is the first report of an EVN arising from the VIIIth cranial nerve with malignant progression.

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Section: Discussioncontrasting

confidence: 48%

Section: Discussioncontrasting

confidence: 46%

Malignant progression of an extraventricular neurocytoma arising from the VIIIth cranial nerve: A case report and literature review

et al. 2018

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“…To investigate sample stability, samples were assessed using the successor Methylation BeadChip (EPIC) array or whole-genome bisulfite sequencing. Established molecular characteristics of the WNT subgroup (CTNNB1 mutations, chromosome 6 loss), MYC and MYCN amplifications, and chromosome 17 status were assessed as previously described (13,(21)(22)(23)(24)27). Each MB subgroup was assessed by immunohistochemistry and mRNA expression signature assays.…”

Section: Dna Methylation Profiling Of the Saudi Mb Cohortmentioning

confidence: 99%

“…These distinct genetic features lead to diverse clinical outcomes (5,7,18,20). Patients with WNT-MB have an excellent prognosis with current therapy schemes (5-years event-free survival ≥90%) and are considered for the controlled reduction of treatment to minimize radiation and chemotherapy exposure (21)(22)(23)(24)(25). The prognoses of SHH-activated MBs are less favorable; SHH-MBs have an intact blood-brain barrier (BBB) and are less responsive to chemotherapy compared to WNT-MBs (22,26,27).…”

Section: Introductionmentioning

confidence: 99%

“…Patients with WNT-MB have an excellent prognosis with current therapy schemes (5-years event-free survival ≥90%) and are considered for the controlled reduction of treatment to minimize radiation and chemotherapy exposure (21)(22)(23)(24)(25). The prognoses of SHH-activated MBs are less favorable; SHH-MBs have an intact blood-brain barrier (BBB) and are less responsive to chemotherapy compared to WNT-MBs (22,26,27). Many SHH-MBs are age-dependent, with those aged ≥17 months more likely to harbor SMO and PTCH1 mutations (18,(28)(29)(30)(31)(32).…”

Section: Introductionmentioning

confidence: 99%

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Methylation Profiling of Medulloblastoma in a Clinical Setting Permits Sub-classification and Reveals New Outcome Predictions

et al. 2020

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Medulloblastoma (MB) is the most common childhood malignant brain tumor and is a leading cause of cancer-related death in children. DNA methylation profiling has rapidly advanced our understanding of MB pathogenesis at the molecular level, but assessments in Saudi Arabian (SA)-MB cases are sparse. MBs can be sub-grouped according to methylation patterns from FPPE samples into Wingless (WNT-MB), Sonic Hedgehog (SHH-MB), Group 3 (G3), and Group 4 (G4) tumors. The WNT-MB and SHH-MB subgroups are characterized by gain-of function mutations that activate oncogenic cell signaling, whilst G3/G4 tumors show recurrent chromosomal alterations. Given that each subgroup has distinct clinical outcomes, the ability to subgroup SA-FPPE samples holds significant prognostic and therapeutic value. Here, we performed the first assessment of MB-DNA methylation patterns in an SA cohort using archival biopsy material (FPPE n = 49). Of the 41 materials available for methylation assessments, 39 could be classified into the major DNA methylation subgroups (SHH, WNT, G3, and G4). Furthermore, methylation analysis was able to reclassify tumors that could not be sub-grouped through next-generation sequencing, highlighting its superior accuracy for MB molecular classifications. Independent assessments demonstrated known clinical relationships of the subgroups, exemplified by the high survival rates observed for WNT tumors. Surprisingly, the G4 subgroup did not conform to previously identified phenotypes, with a high prevalence in females, high metastatic rates, and a large number of tumor-associated deaths. Taking our results together, we demonstrate that DNA methylation profiling enables the robust sub-classification of four disease sub-groups in archival FFPE biopsy material from SA-MB patients. Moreover, we Alharbi et al. Clincal Methylation Profiling of Medulloblastomashow that the incorporation of DNA methylation biomarkers can significantly improve current disease-risk stratification schemes, particularly concerning the identification of aggressive G4 tumors. These findings have important implications for future clinical disease management in MB cases across the Arab world.

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Role of DNMTs in the Brain

Yildiz

Zimmer-Bensch

2022

Advances in Experimental Medicine and Biology

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Medulloblastoma, WNT-activated/SHH-activated: clinical impact of molecular analysis and histogenetic evaluation

Cited by 20 publications

References 51 publications

Malignant progression of an extraventricular neurocytoma arising from the VIIIth cranial nerve: A case report and literature review

Malignant progression of an extraventricular neurocytoma arising from the VIIIth cranial nerve: A case report and literature review

Methylation Profiling of Medulloblastoma in a Clinical Setting Permits Sub-classification and Reveals New Outcome Predictions

Role of DNMTs in the Brain

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