To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.
Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumefactive lesion with unclear pathogenesis. It is diagnosed by pathological findings of the typical histological features that include granular amorphous cores with palisading spindle to epithelioid cells, variable fibrous stroma, foreign-body reaction with giant cells, and calcification/ossification occasionally with psammoma bodies. However, its histopathology may be variable and currently immunohistochemistry plays a limited role in its diagnosis and understanding the pathogenesis. In this study, we examined 6 cases of CAPNONs including 3 intracranial and 3 spinal epidural lesions (age range: 59–69 years; 3 males and 3 females). Immunohistochemistry revealed that all CAPNON cores contain abundant positive deposits of neurofilament protein (NFP), which was supported by electron microscopy finding of filaments (8–13 nm in diameter). In comparison, no NFP positivity was found in 5 psammomatous/metaplastic meningiomas or 7 intervertebral tissue lesions with calcification/ossification. In addition, CAPNON cellular areas showed variable numbers of CD8+ cytotoxic T-cells with less CD4+ T-cells and a decreased ratio of CD4/CD8+ cells, versus the intervertebral tissue lesions without CD8+ or CD4+ cells. Our findings suggest that NFP may be a principal constituent of CAPNONs, and thus involved in the pathogenesis of CAPNON. Given the decreased CD4/CD8 ratio, the pathogenic process of CAPNON is possibly immune- mediated.
The presentation will enable the learner to:
1. Discuss histopathological features of calcifying pseudoneoplasm of the neuraxis (CAPNON) with variation of non-core components.
2. Explore diagnostic and pathogenic roles of immunohistochemical markers including neurofilament protein and CD4/CD8 in CAPNON.
Email your librarian or administrator to recommend adding this to your organisation's collection.