The Vehicle, Fall 2010

Table of ContentsPoetryFill Your Mouth with BerriesAaron Whitepage 1 RelationsJamie Van Allenpage 2 ExodusMegan Marie Olsonpage 4 Single FileRashelle McNairpage 7 The Aesthetic Value of the Moon, by CandlelightKathy Deckerpage 15 FactalsGabrielle Keigherpage 16 Day 5David Jacksonpage 17 Esta LloviendoHeather Gerrishpage 19 FacebrokeDarrin Gordonpage 23 5:08 pmNikki Riechertpage 24 Train TunnelsAshton Tembypage 34 VariationsKathy Deckerpage 35 WantRashelle McNairpage 36 FriendshipScott Maypage 37 Golden LandJacob Swansonpage 38 Last Night I DreamtAshton Tembypage 39 Smallest GestureScott Maypage 44 Somebody\u27s Hut in MexicoGinamarie Lobiancopage 45 Some Things You Just Can\u27t Tap Dance AroundClint Walkerpage 53 Prose Lamparus de DiosAaron Whitepage 8 Learning CurveScott Maypage 18 RocktonKatelyn Pfaffpage 20 Fatal DistractionSolomohn Ennispage 25 Noodle NonsenseGabrielle Keigherpage 41 AntarcticaMichael Payeapage 46 Special Features James K Johnson Award Winners: God is GraciousJohn Klyczekpage 57 To My Ever Growing ChestJennifer Hindespage 74 God\u27s ScapegoatJennifer Hindespage 76 Rape (Verb, Noun)Jennifer Hindespage 78 Featured Artist: Ashton Tembypage 81 Editor\u27s Pick: The Shooter by Patrick Hallpage 87 Chapbook 2010 Author:Kim Hunter-Perkinspage 114 About the Contributorspage 118 About the Editorspage 122https://thekeep.eiu.edu/vehicle/1092/thumbnail.jp

The Vehicle, Fall 2010

Table of ContentsPoetryFill Your Mouth with BerriesAaron Whitepage 1 RelationsJamie Van Allenpage 2 ExodusMegan Marie Olsonpage 4 Single FileRashelle McNairpage 7 The Aesthetic Value of the Moon, by CandlelightKathy Deckerpage 15 FactalsGabrielle Keigherpage 16 Day 5David Jacksonpage 17 Esta LloviendoHeather Gerrishpage 19 FacebrokeDarrin Gordonpage 23 5:08 pmNikki Riechertpage 24 Train TunnelsAshton Tembypage 34 VariationsKathy Deckerpage 35 WantRashelle McNairpage 36 FriendshipScott Maypage 37 Golden LandJacob Swansonpage 38 Last Night I DreamtAshton Tembypage 39 Smallest GestureScott Maypage 44 Somebody\u27s Hut in MexicoGinamarie Lobiancopage 45 Some Things You Just Can\u27t Tap Dance AroundClint Walkerpage 53 Prose Lamparus de DiosAaron Whitepage 8 Learning CurveScott Maypage 18 RocktonKatelyn Pfaffpage 20 Fatal DistractionSolomohn Ennispage 25 Noodle NonsenseGabrielle Keigherpage 41 AntarcticaMichael Payeapage 46 Special Features James K Johnson Award Winners: God is GraciousJohn Klyczekpage 57 To My Ever Growing ChestJennifer Hindespage 74 God\u27s ScapegoatJennifer Hindespage 76 Rape (Verb, Noun)Jennifer Hindespage 78 Featured Artist: Ashton Tembypage 81 Editor\u27s Pick: The Shooter by Patrick Hallpage 87 Chapbook 2010 Author:Kim Hunter-Perkinspage 114 About the Contributorspage 118 About the Editorspage 122https://thekeep.eiu.edu/vehicle/1092/thumbnail.jp

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 x 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 x 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 x 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 x 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 x 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 x 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

We performed a multistage genome-wide association study (GWAS) including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT; per-allele odds ratio [OR] = 0.79; 95% confidence interval [CI] = 0.74–0.84; P = 3.0×10−12), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2; OR = 1.46; 95% CI = 1.30–1.65; P = 1.1×10−10), rs9581943 at 13q12.2 (PDX1; OR = 1.15; 95% CI = 1.10–1.20; P = 2.4×10−9), and rs16986825 at 22q12.1 (ZNRF3; OR = 1.18; 95% CI = 1.12–1.25; P = 1.2×10−8). An independent signal was identified in exon 2 of TERT at the established region 5p15.33 (rs2736098; OR = 0.80; 95% CI = 0.76–0.85; P = 9.8×10−14). We also identified a locus at 8q24.21 (rs1561927; P = 1.3×10−7) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study has identified multiple new susceptibility alleles for pancreatic cancer worthy of follow-up studies

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

MEDULLOBLASTOMA

BACKGROUND: LMD in children with recurrent medulloblastoma and other PNETs carries a poor prognosis and novel therapies are urgently needed to improve disease control. Somatostatin receptor-2 (SSR-2)is overexpressed in medulloblastoma and other central PNETs and can serve as a target for radionuclide tagged somatostatin analogues like 177Lu-DOTA-TATE that has shown considerable efficacy in adults with SSR-2 positive neuro-endocrine tumors. As a preliminary step prior to testing this agent in children with LMD, we performed an efficacy study of i.t. 177Lu-DOTA-TATE in athymic rats bearing LMD from MBL. METHODS: The subarachnoid space was accessed through the animal's cervical spine and a catheter was threaded along the dorsal aspect of spinal cord to the lumbar region and injected with 1 x 107 D341 human MBL cells and treatment initiated 3 days later. Groups of 10 animals received a single i.t. dose of 2, 3, or 5 mCi of 177Lu- DOTA-TATE or saline control. Animals were followed 300 days for survival. RESULTS: Treatment with 2 mCi resulted in an increase in median survival of 58.3% compared with saline control (p < 0.001). Treatment with 5.0 mCi of 177Lu-DOTA-TATE increased median survival by 75.0% compared with the saline control group while a single dose of 3.0 mCi 177Lu-DOTA-TATE increased median survival compared with saline controls by 519.4%. Long-term survivors were seen in 0 of 10 animals treated with saline, 4 of 11 treated with 3 mCi, and 3 of 12 treated with 5.0 mCi. CONCLUSION: Intrathecal 177Lu- DOTA TATE is efficacious in controlling LMD from medulloblastoma in athymic rats. A phase I trial of this agent is being planned in children with LMD from recurrent MBL and other CNS PNETs. INTRODUCTION: Medulloblastoma/PNET is the most common malignant brain tumor in children. For children older than 3 years, the treatment of high risk group includes surgery, craniospinal (CSI) radiation therapy (30-36 Gy) plus local boost radiotherapy (54-56 Gy) and adjuvant chemotherapy, such as cisplatinum, carboplatin, lomustine, cyclophosphamide, and vincristine. The results have demonstrated 5-year overall survival (OS) of 40-60%. This study aimed to evaluate the outcomes of high risk medulloblastoma/PNET patients who were treated with radiation and adjuvant chemotherapy. METHODS: Patients were diagnosed with high risk medulloblastoma/PNET according to the histopathology, medulloblastoma risk classification by an evidence of metastasis or the residual tumor more than 1.5 cm2 and evidence of residual tumor after surgery in PNET. Treatment protocol was CSI RT 36 Gy with local boost at tumor 54-56 Gy. Two to four weeks after RT, patients received 8 courses of chemotherapy consisting of cyclophosphamide 800 mg/m2, day 1-3 and vincristine 2 mg/m2, week 1-3, alternated with carboplatin 200 mg/m2, day 1-3 and etoposide 150 mg/m2, day 1-3. RESULTS: Total of 25 patients, male: female of 2.6:1 and mean ± SD for age of 9.7± 3.0 years, were enrolled. The 5-year progression free survival and OS were 41.6± 11.7% and 61.5± 12.9%,respectively. The age and sex did not determine the difference in outcomes. The hematotoxic side effect, according to the National Cancer Institute's Common Terminology Criteria, were grade 4 leucopenia 60%, grade 4 neutropenia 60%, grade 4 anemia 20%, grade 4 thrombocytopenia 16%, grade 3 leucopenia 20%, grade 3 neutropenia 20%, grade 3 anemia 40%, and grade 3 thrombocytopenia 36%. Febrile neutropenia was found in 11 patients (44%). CONCLUSION: The present study demonstrated the similar outcomes of high risk medulloblastoma/PNET with the previous studies. Although, the grade 3 and 4 hematologic toxicity was high, no treatment related death was found. OBJECTIVE: Recent investigations revealed an association between transcriptional subtypes and morphological features in medulloblastoma. Since both characteristics are of prognostic significance, a precise correlation between them should be well established. Therefore we re-examined paediatric nodular medulloblastoma tumours for correlation with molecular subtypes of disease. METHODS: Paediatric patients with previously diagnosed desmoplastic/nodular (D/N) or medulloblastoma with extensive nodularity (MBEN) histopathology were re-analysed by two neuropathologists. In addition to H&E-stained slides, reticulin preparations were simultaneously analysed from the same FFPE blocks. For identification of transcriptional subtypes of tumours immunohistopathological analyses were performed using a panel of representative antibodies. MYCC amplification was detected by FISH. RESULTS: Altogether 28 tumours with original MBEN or D/N diagnosis where molecular subtypes could be determined were identified. All tumours with MBEN histology belonged to SHH group and displayed distinctive reticulin-positive internodular reaction. However, only ∼60% of tumours with original D/N diagnosis were reticulin-positive. They belonged to SHH type, were mainly infantile and patients are still alive. Among reticulin-negative tumours only two were of the SHH type and were subsequently reclassified as classic and anaplastic tumours with pseudonodules. Importantly, all remaining reticulin-negative tumours with a presence of nodules in H&E staining belonged to the non-WNT,SHH type. Therefore the original diagnosis was again reclassified as classic or anaplastic tumours with pseudonodules. Patients from this group were only males, with median age 14 years old, one had MYCC amplification and two of them died because of disease. Therefore, non-WNT,SHH tumours did not display typical desmoplastic/nodular histology accompanied by reticulin positive reaction as opposite to truly D/N tumours being typical for SHH molecular group (p < 0.001). CONCLUSION: Reticulin staining is necessary to distinguish two different biologically and clinically group of nodular tumours which appear morphologically similar under H&E staining alone. BACKGROUND: In the PNET4 European randomised controlled trial, children with standard risk medulloblastoma were allocated to HFRT or to STRT. All received maintenance chemotherapy. Event-free survival was similar between the two treatment arms. HFRT was associated with worse growth and better questionnaire-based executive function 6.1 years post-diagnosis, especially in children aged <8 years at diagnosis (Kennedy et al., IJROBP, 2014). Therefore the aim of this study was to compare cognitive outcomes between treatment arms. METHODS: Neuropsychological data was collected prospectively in 137 patients from Germany, France, Italy and Sweden. Using results of the Wechsler Intelligence Scales, Kaufman Assessment Battery for Children, and Raven's progressive matrices, we generated: Full scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ), working memory index (WMI) and speed of processing index (PSI). RESULTS: Among the 137 participants, [n = 71 HFRT, n = 66 STRT, 63.5% males; mean (SD, range) age at diagnosis 9.3 years (3.2, 4 to 17.6), 40.9% aged <8 years at diagnosis; age at assessment 15.6 years (3.7, 8.3 to 25). Mean (SD, range) FSIQ in all participants was 88 (19, 40-137); mean intergroup difference [95% CIs] (3.88, [-2.66 to 10.41], p = .24). No difference was found in children aged > 8 years at diagnosis. In children aged <8 at diagnosis, VIQ was significantly higher in children receiving HFRT compared to STRT; a similar trend was found for PSI but not for PIQ,WMI and FSIQ (mean inter-group differences [95% CIs]): VIQ 12.02 [2.37 to 21.67], p = 0.02; PIQ (2.73 [-7.89 to 13.35], p > .10); WMI (5.20 [-2.07 to 12.47], p > .10), PSI (10.91 [-1.54 to 23.36], p = .08; FSIQ (5.28 [-4.23 to 14.79], p > .10). CONCLUSION: HFRT was associated with higher verbal IQ in children aged <8 years at diagnosis, consistent with the previous report using questionnaire-based data. Effect sizes were small, albeit with 10 point inter-group differences within their 95% CIs. Preoperative chemotherapy is often used in pediatric oncology to treat metastatic disease and facilitate the surgery of the primary tumor, but not for brain tumors. A first pilot study showed in 2004 the feasibility and effectiveness of preoperative chemotherapy in treating high-risk medulloblastomas. Seventy-one patients were treated for a metastatic medulloblastoma between 2002 and 2010 at Gustave Roussy. Two strategies were compared in intention to treat. Forty-two children were operated at the time of the diagnosis (group A) and the 29 others children were treated with 2 courses of carboplatin and etoposide (group B) after histological diagnosis (biopsy) and before a delayed surgery. Children of group A received the two courses of carboplatin and etoposide afterwards. The rest of the protocol (high-dose chemotherapy and cranio-spinal irradiation) was similar in the both groups. Complete neuropsychological testing, including intelligence quotient measurements, was scheduled before surgery, before radiotherapy and every year thereafter. MRI performed after neo-adjuvant chemotherapy showed an objective response in 24 patients (83%) and a stable disease in 4 patients (14%). Complete excision rate was significantly higher in group B (100% versus 64%, p = 0.00248) without any difference in postoperative complication rate. Medulloblastoma cells could still be evidenced despite preoperative chemotherapy. The median Total Intelligence Quotient (TIQ) was 81 and 90 in group A and B respectively (p = 0.02543). This difference was even more significant in young children (77 vs 91 points for groupe A and B, respectively). Hydrocephalus and brain radiotherapy dose were not associated with TIQ. Neo-adjuvant chemotherapy had no negative impact on local disease control (79 versus 83%). Event-free survival and overall survival at 3 years were 54 versus 62% and 58 versus 68% respectively (p = NS). Neo-adjuvant chemotherapy in metastatic medulloblastoma is safe and could have a positive impact on neuropsychological outcome and completeness of surgery. BACKGROUND: We prospectively evaluated histopathological findings and molecular variables, which have shown to impact prognosis of medulloblastoma patients, for outcome prediction in homogenously treated metastatic medulloblastoma patients. METHODS: One hundred twenty-three patients aged 4-21 years, diagnosed from 2001 to 2007, received systemic induction chemotherapy and intraventricular methotrexate, followed by hyperfractionated radiotherapy, and maintenance chemotherapy. From 86 patients paraffin material was available for immunohistochemical analysis to determine the activation status of the wingless (WNT) pathway, by immunostaining for β-catenin and sequencing of CTNNB1. In 81 of those 86 patients, material was available for gene amplification assessment of MYCC and MYCN by multiplex ligation-dependent probe amplification. RESULTS: Tumors with nuclear β-catenin immunopositivity showed excellent outcome (n = 4, all classic histology, 3 / 4 with CTNNB1 mutation; 5-year event-free (EFS) and overall survival (OS): 100%) compared to patients with tumors lacking nuclear β-catenin staining (n = 82; 5-year rates: 63% and 72%, respectively; p = 0.134 for EFS, p = 0.213 for OS). Patients with tumors characterized by MYC amplification (n = 5; MYCC, n = 2; MYCN, n = 3; all classic histology despite one case with MYCC amplification showing large cell histology) had poor outcome (20% for EFS and OS, respectively) when compared to patients with non-MYCC/MYCN amplified tumors (n = 76; 5-year EFS and OS: 65% and 75%, respectively; p = 0.011 for EFS, p < 0.001 for OS). Based on histopathological and molecular findings, we identified three risk groups: Favorable- (β-catenin nucleopositive and/or desmoplastic histology (n = 7; one death of disease), n = 11; 5-year EFS and OS 89 ± 11%), poor- (MYCC/MYCN amplification and/or anaplastic or large cell histology, n = 6; 5-year EFS and OS 33 ± 19%), and intermediate-risk group (n = 64; 5-year EFS and OS 61 ± 7%, and 72 ± 6%, respectively; p = 0.020 for EFS, and p = 0.002 for OS). CONCLUSION: Histopathological subtyping together with molecular features (WNT pathway and MYCC/MYCN amplification status) differentiate three risk groups in homogenously treated metastatic medulloblastoma patients. Supported by Deutsche Kinderkrebsstiftung. BACKGROUND: A number of different second neoplasms have been reported in patients with neuroblastoma including brain tumors. None of these second cancers have occurred with sufficient frequency to indicate a specific relationship between neuroblastoma and any other neoplasm except in rare cancer syndromes. OBJECTIVE: We report a case of medulloblastoma in a child 5 months after successful treatment of metastatic neuroblastoma. DESIGN AND METHOD: A MEDLINE search was conducted for queries including “Children”, “medulloblastoma” and ‘neuroblastoma”. Relevant papers were selected for literature review. RESULT: A 10 months old female presented with 2-month history of right eye proptosis. CT scan of the abdomen showed a right adrenal mass with liver metastasis. Brain MRI revealed disease at the right orbital fossa extends to middle cranial fossa with no intracranial disease. Pathology of the right adrenal mass confirmed neuroblastoma with non amplified N myc. The patient was classified as intermediate risk disease and started on chemotherapy consisted of vincristine, cyclophosphamide, cisplatin, dacarbazine, ifosphamide and Adriamycin followed by 5 cycles of Accutane. Surveillance MIBG revealed no evidence of residual disease. Five months later, she had a new onset of trouble walking. CT and MRI of the brain showed a mass in the right cerebellar hemisphere with hydrocephalus. Complete Surgical resection of the mass was done and pathology revealed anaplastic medullobastoma. The patient initiated chemoradiation treatment for medulloblastoma. Her treatment was stopped because of disseminated fungal infection. She is currently receiving metronomic therapy with cyclophosphamide and topotecan and has been clinically stable. Molecular genetic tests are pending for familial cancer syndromes. CONCLUSION: We report a case of metachronous medullobastoma after treatment of metastatic neuroblastoma in a two year-old child. The occurrence of metachronous neoplasms is rare and challenging to treat. Cancer familial syndromes like neurofibromatosis type 1 and Simpson-Golabi-Behmel syndrome need to be excluded. Group 3 medulloblastoma with elevated c-MYC has the worst prognoses of the four molecular subgroups. To generate a genetically defined model of this disease, we transformed human fetal cerebellar stem cells with MYC along with hTERT, dominant negative p53 and constitutively active AKT. The resulting xenografts showed morphological similarities to large cell/anaplastic medulloblastoma, leptomeningeal and spinal dissemination, and had a gene expression profile closely aligned with Group 3 primary tumors. Because MYC over-expression leads to increased glutamine metabolism and glutamine addiction in other cancers, we hypothesized that MYC-driven MB would exhibit increased glutamine metabolism and be sensitive inhibitors of glutamine metabolism. In both our human stem cell derived and established medulloblastoma cell lines, MYC expression positively correlates with increased expression of glutaminolytic enzymes. Inhibition of glutamine metabolism was achieved using two glutamine analogs, acivicin and 6-diazo-5-L-norleucine (DON). In our human stem cell models, MYC-transformed cells experienced a significant decrease in proliferation and an increase in apoptosis after acivicin treatment (p < 0.005), while SV40-transformed cells were unaffected. Both compounds also significantly decreased growth and increased apoptosis of the high-MYC MB cell lines D425Med and D283Med. In xenograft experiments using D283Med, fewer mice receiving acivicin developed flank tumors, and the resulting tumors were significantly smaller (80.9 mm3 treated vs 273.8 mm3 untreated). Glutaminase knockdown using short hairpins also significantly decreased growth of D425Med and D283Med. In summary, we present a novel human cerebellar stem cell based model of Group 3 medulloblastoma, and data suggesting that glutamine metabolism may be a therapeutic target in MYC-driven MB