Disease relevance of Medulloblastoma

• In keeping with the role of PTCH as a tumor-suppressor gene, somatic mutations of this gene occur in sporadic basal-cell carcinomas and medulloblastomas [1].
• These results provide the first insight into the genetic regulation of medulloblastoma metastasis and are the first to suggest a role for PDGFRA and the RAS/MAPK signaling pathway in medulloblastoma metastasis [2].
• Increased melphalan activity in intracranial human medulloblastoma and glioma xenografts following buthionine sulfoximine-mediated glutathione depletion [3].
• Enhancement of nitrosourea activity in medulloblastoma and glioblastoma multiforme [4].
• Because accumulating evidence supports an association between JCV infection and human brain tumors, including medulloblastomas, we assessed the presence of JCV Agno gene sequences and the expression of agnoprotein in a series of 20 well-characterized medulloblastomas [5].

Psychiatry related information on Medulloblastoma

• We report a confirmatory case of sudden, severe visual loss in association with cerebellar mutism after resection of a midline medulloblastoma in a 7-year-old [6].

High impact information on Medulloblastoma

• PDGFRB is overexpressed in metastatic medulloblastoma [7].
• Mutations in SUFU predispose to medulloblastoma [1].
• SUFU is a newly identified tumor-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway through a newly identified mechanism [1].
• Inhibitors of PDGFRA and RAS proteins should therefore be considered for investigation as possible novel therapeutic strategies against medulloblastoma [2].
• We have used representational difference analysis to identify a homozygous deletion at 10q25.3-26.1 in a medulloblastoma cell line and have cloned a novel gene, DMBT1, spanning this deletion [8].

Chemical compound and disease context of Medulloblastoma

• BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect [9].
• PURPOSE: This study was designed to determine whether resistance to the activity of nitrosourea (the drug BCNU) in BCNU-resistant human medulloblastoma (D341 Med) and human glioblastoma multiforme (D-456 MG) can be reversed by the methylating agent streptozocin and the O6-substituted guanines O6-methylguanine and O6-benzylguanine [4].
• In the desmoplastic variant of medulloblastoma, PAX5 expression was restricted to the reticulin-producing proliferating tumor areas containing undifferentiated cells; PAX5 was not expressed in the reticulin-free nonproliferating islands undergoing neuronal differentiation [10].
• Carboplatin and cisplatin in medulloblastoma at diagnosis: "comparable efficacy?" [11].
• Cyclophosphamide resistance in medulloblastoma [12].

Biological context of Medulloblastoma

• These data suggest that deregulated expression of PAX5 correlates positively with cell proliferation and inversely with neuronal differentiation in desmoplastic medulloblastoma [10].
• REN(KCTD11) seems to inhibit medulloblastoma growth by negatively regulating the Hedgehog pathway because it antagonizes the Gli-mediated transactivation of Hedgehog target genes, by affecting Gli1 nuclear transfer, and its growth inhibitory activity is impaired by Gli1 inactivation [13].
• In this study, we found that many human medulloblastomas express significantly elevated levels of both myc oncogenes, regulators of neural progenitor proliferation, and REST/NRSF, a transcriptional repressor of neuronal differentiation genes [14].
• We have characterized the genomic structure of PTCH2 and have used single-stranded conformational polymorphism analysis to search for mutations in PTCH2 in NBCCS patients, basal cell carcinomas and in medulloblastomas [15].
• Gene expression analyses showed that OTX2 transcripts were present at high levels in 14 of 15 (93%) medulloblastomas with anaplastic histopathologic features [16].

Anatomical context of Medulloblastoma

• Five relapses (in 5 patients) occurred (1 optic nerve glioma, 2 medulloblastomas, and 2 ependymomas), three during and two after completion of GH treatment [17].
• This study evaluated the use of high-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue (ASCR) in patients with recurrent medulloblastoma [18].
• We found that Shh pathway activity was suppressed in medulloblastoma cells cultured in vitro and it was not restored when these cells were transplanted into the flank of nude mice [19].
• Medulloblastoma occurs as part of Turcot's syndrome, and patients with Turcot's who develop medulloblastomas have been shown to harbor germ-line APC mutations [20].
• A novel role for extracellular signal-regulated kinase 5 and myocyte enhancer factor 2 in medulloblastoma cell death [21].

Gene context of Medulloblastoma

• Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease [2].
• The tumor suppressors Ink4c and p53 collaborate independently with Patched to suppress medulloblastoma formation [22].
• In human medulloblastomas reverse transcription-PCR for Shh and Notch targets revealed activation of both of these pathways in most tumors when compared with normal cerebellum [23].
• Mutations in CTNNB1 were found exclusively among medulloblastomas that demonstrated nuclear beta-catenin immunoreactivity, but no evidence of APC mutation was found in these cases [24].
• Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched [25].

Analytical, diagnostic and therapeutic context of Medulloblastoma

• A collection of 23 medulloblastomas was analyzed for expression of the developmental control genes of the PAX and EN gene families by RNase protection and in situ hybridization [10].
• These results support our laboratory studies demonstrating melphalan activity in human medulloblastoma, suggest that similar activity may be demonstrated against pineoblastoma, and support further trials with this agent (administered prior to radiotherapy) in the treatment of patients with newly diagnosed poor-prognosis medulloblastoma [26].
• Immunohistochemistry revealed strong expression of PPM1D in 148 (88%) of 168 and CDK6 in 50 (30%) of 169 medulloblastomas [27].
• CONCLUSION: WMLs in medulloblastoma or PNET patients treated with conformal radiotherapy and HDC are typically transient and asymptomatic, and may mimic early tumor recurrence [28].
• These results extend our previous studies demonstrating the antitumor activity of nitrogen and phosphoramide mustard-based bifunctional alkylating agents in the treatment of human medulloblastoma continuous cell lines and transplantable xenografts, and support the continued use of these agents in clinical trials [29].

References