Medulloblastoma subgroups remain stable across primary and metastatic compartments

Abstract Medulloblastoma comprises four distinct molecular variants with distinct genetics, transcriptomes, and outcomes. Subgroup affiliation has been previously shown to remain stable at the time of recurrence, which likely reflects their distinct cells of origin. However, a therapeutically relevant question that remains unanswered is subgroup stability in the metastatic compartment. We assembled a cohort of 12-paired primary-metastatic tumors collected in the MAGIC consortium, and established their molecular subgroup affiliation by performing integrative gene expression and DNA methylation analysis. Frozen tissues were collected and profiled using Affymetrix gene expression arrays and Illumina methylation arrays. Class prediction and hierarchical clustering were performed using existing published datasets. Our molecular analysis, using consensus integrative genomic data, establishes the unequivocal maintenance of molecular subgroup affiliation in metastatic medulloblastoma. We further validated these findings by interrogating a non-overlapping cohort of 19 pairs of primary-metastatic tumors from the Burdenko Neurosurgical Institute using an orthogonal technique of immunohistochemical staining. This investigation represents the largest reported primary-metastatic paired cohort profiled to date and provides a unique opportunity to evaluate subgroup-specific molecular aberrations within the metastatic compartment. Our findings further support the hypothesis that medu...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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aliga S, Yeap BY, Berrington de Gonzalez A, Yock TI Abstract OBJECTIVE: The Pediatric Proton/Photon Consortium Registry (PPCR) is a comprehensive data registry composed of pediatric patients treated with radiation. It was established to expedite outcomes-based research. The attributes which allow the PPCR to be a successful collaboration are reviewed. METHODS AND MATERIALS: Current eligibility criteria are radiotherapy patients
Source: The British Journal of Radiology - Category: Radiology Authors: Tags: Br J Radiol Source Type: research
Nature, Published online: 09 October 2019; doi:10.1038/s41586-019-1650-0Recurrent non-coding U1-snRNA mutations drive cryptic splicing in Shh medulloblastoma
Source: Nature AOP - Category: Research Authors: Source Type: research
i Infante Di Marcotullio : Pharmacological Hedgehog (Hh) pathway inhibition has emerged as a valuable anticancer strategy. A number of small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector glioma-associated oncogene 1 (Gli1) has been designed and developed. In a recent study, we exploited the high versatility of the natural isoflavone scaffold for targeting the Hh signaling pathway at multiple levels showing that the simultaneous targeting of Smo and Gli1 provided synergistic Hh pathway inhibition stronger than single administration. This approach seems to ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Planta Med DOI: 10.1055/a-1013-0382In Europe, especially in German-speaking countries, administration of mistletoe extracts is the most common and popular complementary and alternative therapy approach reported in oncology. Mistletoe therapy is applied to children with cancer for curative and palliative therapeutic regimes with increasing frequency, but at the same time, there are only a few studies on the effectiveness of this therapy. Therefore, we have investigated the response of various pediatric cell lines (acute myeloid leukemia, Ewingʼs sarcoma, hepatocellular carcinoma, medulloblastoma, neuroblastoma, and osteosa...
Source: Planta Medica - Category: Drugs & Pharmacology Authors: Tags: Original Papers Source Type: research
Abstract Yap/Taz are well-established downstream effectors of the Hippo pathway, known to regulate organ size by directing proliferation and apoptosis. Although the functions of Yap/Taz have been extensively studied, little is known about their role in brain development. Here, through genetic ablation, we show that Yap/Taz are required for cerebellar morphogenesis. Yap/Taz deletion in neural progenitors causes defects in secondary fissure formation, leading to abnormal folia development. Although they seemed very likely to serve an important function in the development of cerebellar granule cell precursors, Yap/Ta...
Source: Developmental Biology - Category: Biology Authors: Tags: Dev Biol Source Type: research
Oncogene, Published online: 03 October 2019; doi:10.1038/s41388-019-1036-7EZH2 targeting reduces medulloblastoma growth through epigenetic reactivation of the BAI1/p53 tumor suppressor pathway
Source: Oncogene - Category: Cancer & Oncology Authors: Source Type: research
Cerebrospinal fluid (CSF) leak is a common complication after cranial surgery. Therefore, after neurosurgical procedures it is crucial to obtain a dural repair that is complete and watertight. There are many techniques that have been described attempting to achieve this goal. However, there are complicating factors (eg, poor tissue viability, need for future radiation, comorbidities, infection, size of the dural defect, multiple operations) that may require a more comprehensive approach to achieve an optimal healing environment. The authors present a technique that uses a muscle free flap to vascularize an autologous fasci...
Source: Journal of Craniofacial Surgery - Category: Surgery Tags: Brief Clinical Studies Source Type: research
AbstractBackgroundHigh-dose chemotherapy combined with autologous stem cell rescue (HDCT+ASCR) has been used to treat newly diagnosed medulloblastoma (MB), but there was no high-level evidence to support its efficacy.MethodsDatabases were retrieved, and patients were divided into two groups: group A was radiotherapy combined with HCDT+ASCR, and group B was classical radiotherapy and chemotherapy. The clinical benefit rate, progression-free survival (PFS), total survival (OS) and toxicities data were extracted.Results22 clinical trials met the inclusion criteria, 416 in group A and 2331 in group B. There was no difference i...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
AbstractBackgroundMedulloblastoma (MB) is a rare central nervous system malignancy in adult. For its rarity, most previous studies are limited on patient populations and ascertainment bias. We aimed to explore the population-level trends in incidence and assess potential predictors of overall survival (OS).MethodsWe utilized the Surveillance, Epidemiology and End Results Program (SEER) database between 1973 and 2015, to estimate the epidemiological trends of adult MB in the United States. Propensity-score matching was used to balance potential selection biases and Cox proportional hazard modeling was used to determine pred...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsRe-irradiation for recurrent pediatric medulloblastoma can offer some patients disease control, particularly those with focally recurrent disease in the brain. Prospective studies are needed to confirm subgroups of patients who may benefit most from RT2.
Source: Journal of Neuro-Oncology - Category: Cancer & Oncology Source Type: research
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