Scientific Projects- Biospecimen

Scientific Projects- Biospecimen

The CBTTC strives to provide high-quality biospecimens with annotated clinical and genomic data to facilitate and advance childhood brain tumor research. Investigators do not have to be part of the CBTTC to submit a scientific proposal to the CBTTC Scientific Committee. If the Scientific Committee approves the proposal, materials are provided without charge to that investigator on the condition that all data generated will be shared with the CBTTC. The CBTTC is accepting scientific proposals that require specimen use through August 15, 2018. The next submission period will begin on November 1, 2018. Data access proposals are accepted at any time.

This process includes a review of the project proposal first by primary reviewers with expertise related to the proposal and then by the entire scientific committee. In this way, the committee can maximize the use of very limited amounts of each sample for evaluation.

Additionally, a rigorous quality-control check is performed on the specimens and clinical data before the scientific committee reviews or releases any material.

DNA and RNA extractions are conducted by the Biorepository Core at Children’s Hospital of Philadelphia to ensure standardization, with the exception of special requests. Genomic sequencing may be performed at CHOP by the Sequencing Core Facility (BGI@CHOP) or a facility identified by the investigator.

To date, approximately 850 whole genomes, 350 RNA profiles, and 20 miRNA profiles have been sequenced.

To query specimens annotated with clinical data visit the CBTTC Clinical Data and Specimen Inventory Portal

To access the online proposal system and submit a scientific project for data or specimens, please click the button below

Submit a Scientific Project


CBTTC Approved Biospecimen Scientific Projects

To contact an investigator or to submit questions related to a CBTTC scientific project, please email research@cbttc.org 

Project 1: Whole Genome Sequencing of Low-Grade Glioma and Ganglioglioma

Principal Investigator(s): Adam Resnick Ph.D. Assistant Professor of Neurosurgery at Children’s Hospital of Philadelphia
Diagnosis/Classification: Low-grade glioma and ganglioglioma
Project Summary: This project generated 26 Whole Genome Sequencing (WGS) analyses from matched Primary Tumor and Blood-Derived Normal specimens from 13 Low-Grade Glioma (LGG) patients. These data were generated as part of the CBTTC study cohort CBTTC_0001a and made available in April and November of 2014.
Project Sponsor: Voices Against Brain Cancers Foundation
Specimen Data: 26 Whole Genome Sequencing (WGS) analyses from matched Primary Tumor and Blood-Derived Normal specimens from 13 Low-Grade Glioma (LGG) patients.
Project Status: Complete

Project 2: Genomic Investigation of Craniopharyngioma

Principal Investigator(s): Adam Resnick, Ph.D., Assistant Professor of Neurosurgery at Children’s Hospital of Philadelphia
Diagnosis/Classification: Craniopharyngioma
Project Summary: This project is a joint effort between investigators at CHOP, The University of Pennsylvania, and the Dana Farber Foundation and generated These data were generated as part of the CBTTC study cohort CBTTC_0002a and made available in September of 2013. Seeks to identify the genomic characteristics of craniopharyngiomas by means of whole-genome sequencing.
Project Sponsor: Children’s Hospital of Philadelphia
Specimen Data: Whole-genome sequencing of 5 matched pairs of tumor/blood, whole-exome sequencing of 7 tumor/blood, and targeted sequencing of 30 additional formalin-fixed paraffin-embedded craniopharyngioma samples.
Project Status: Complete

Project 3: Genomic Evaluation of Malignant Pediatric Cortical Tumors

Principal Investigator(s): Dr. Sarah Leary, Seattle Children’s Hospital; Angela Waanders, MD, MPH, Children’s Hospital of Philadelphia, Annie A. Huang, MD, Ph.D., FRCP(C), Toronto Hospital for Sick Children
Diagnosis/Classification: Supratentorial primitive neuroectodermal tumor, high-grade glioma, ependymoma
Project Summary: This project aims to describe genomic alterations and tumor subtypes within a large cohort of well-characterized supratentorial malignant pediatric brain tumors. The goal of this project is to evaluate the association between genetically determined subtypes and standard clinical factors such as histology, location, metastatic status, and survival. These data were generated as part of CBTTC study cohorts CBTTC_0003a, CBTTC_0003b and CBTTC_0003c and made available in July of 2015, March 29, 2016, and April 22, 2016.
Project Sponsor: Children’s Brain Tumor Foundation
Specimen Data: This dataset is composed of 70 Whole Transcriptome Sequencing (RNA-Seq) analyses from Primary Tumor specimens from 23 ependymoma patients, 13 supratentorial primitive neuroectodermal tumor (PNET) patients, and 34 high-grade glioma (HGG) patients.
Project Status: Complete

Project 0003e: Advancing Collaborative Pediatric Brain Tumor Research Through Temporally-based Predictive Modeling of a Large-scale National Clinical Data Research Network.

Principal Investigator(s): Alex Felmeister, MS, Drexel University; Angela Waanders, MD, MPH, Children’s Hospital of Philadelphia (CBTTC), Sarah Leary, MD, Seattle Children’s Hospital; L. Charles Bailey, MD, Ph.D., Children’s Hospital of Philadelphia (PEDSNet), Xiaohua Tony Hu, Ph.D., Drexel University
Diagnosis/Classification: Informatics Research: Supratentorial primitive neuroectodermal tumor, high-grade glioma, ependymoma
Project Summary: This research intends to look predictive models based on temporally based observational health data that is sequential in nature from clinical data sets to annotate the complex biology collected from cancer patients – specifically children suffering from highly lethal rare high-grade gliomas. This research focuses on the intersection two national longitudinal health data collection projects: The Children’s Brain Tumor Tissue Consortium (CBTTC) and the PEDSNet Clinical Data Research Network (CDRN) with the intention of harmonizing the two national projects as they grow to aid in the human annotation of biologically based resources with large scale automated health data networks. The research proposed contributes to the coherence broadly defined technical area of cross-platform workflow architectures to facilitate resource sharing and reuse in biomedical research.
Project Sponsor: Coherence at Scale Program led by the Council on Library and Information Resources (CLIR) (http://coherence.clir.org/) funded by the Andrew W. Mellon Foundation.
Specimen Data: N/A (Data-only project)
Project Status: In progress January 1, 2017. Expected completion December 31, 2018

Project 4: Molecular Studies Designed to Examine the Relationship Between the HH Pathway and Nestin, Whole Genome Sequencing of Medulloblastoma, and Genomics of Human Medulloblastoma and AT/RT

Principal Investigator(s): Tom Curran, PhD., FRS, Children’s Mercy Children’s Research Institute (CRI)
Diagnosis/Classification: Medulloblastoma and Atypical Teratoid Rhabdoid Tumor
Project Summary: Project data was generated as part of CBTTC study cohorts CBTTC_0004b, CBTTC_0004c, CBTTC_0004d and CBTTC_0004e and made available in June, May and October of 2015 and May and April of 2016. These data were generated as part of the CBTTC study cohort CBTTC_0004d and made available in April 2016. These data were generated as part of the CBTTC study cohort CBTTC_0004e and made available in April 2016.
Project Sponsor: Make Some Noise, Women Committee, Kourtney Rose Foundation
Specimen Data: This project generated 19 Whole Transcriptome Sequencing (RNA-Seq) and microRNA sequencing analyses, from Primary Tumor specimens and 87 Whole Genome Sequencing analyses from matched Primary Tumor and Blood-Derived Normal specimens from Medulloblastoma patients. Additionally, 12 Whole Genome Sequencing (WGS) analyses from Primary Tumor and Blood-Derived Normal specimens from Atypical Teratoid Rhabdoid Tumor (ATRT) patients were generated.
Project Status: Complete

Project 5: Exploration of IDO1 as a Therapeutic Target in pCNS Tumors

Principal Investigator(s): Rishi Lulla, MD, MS, Ann and Robert Lurie Children’s’ Hospital of Chicago; Derek Wainwright, Ph.D., Northwestern University Feinberg School of Medicine; Craig M. Horbinski, MD, Ph.D., Northwestern University Feinberg School of Medicine
Diagnosis/Classification: Low-grade glioma, High-grade glioma, Medulloblastoma, and Ependymoma
Project Summary: This project, led by Dr. Rishi Lulla and a team of scientists with specific expertise in IDO1, aims to measure the level of IDO1 expression in pediatric CNS tumors, specifically focusing on low-grade glioma, high-grade glioma, medulloblastoma, and ependymoma. Published studies suggest that IDO1 is a promising target for immunotherapy in adult gliomas. However, similar data for pediatric brain tumors is not available and may have significant translational implications in children. The project will continue to expand the potential therapeutic targets for immune-mediated therapies by obtaining expression levels of IDO1 mRNA and DNA which will be used as confirmation for whole-exome and methylation profiling.
Project Sponsor: NIH R00NS082381-04 (Wainwright); Neuro-Oncology Research Fund at Lurie Children’s Hospital.
Specimen Data: DNA and RNA from 10 High-Grade Glioma patients, 10 Low-Grade Glioma patients, 10 Medulloblastoma patients, 9 ependymoma patients, and 6 diffuse intrinsic pontine glioma patients were used for this data generation.
Project Status: In-progress

Project 6: Epigenetic Basis of Gender Differences in Pediatric GBM

Principal Investigator(s): Sheng Li Ph.D., Weill Cornell Brain, and Spine Center; Jeff Greenfield, MD, Ph.D., Weill Cornell Brain and Spine Center
Diagnosis/Classification: High-Grade Glioma
Project Summary: This project aims to profile the transcriptome and epigenome in order to compare these profiles between boys and girls with pediatric GBM to identify lesions that cause the difference in clinical outcomes of these patients.
Project Sponsor: Children’s Brain Tumor Project
Specimen Data: DNA from 10 high-grade glioma patients will be sent for this project and the data will be generated as part of CBTTC study cohort CBTTC_0006a
Project Status: In-progress

Project 7: Validation Cohort – WGS, RNAseq, and Proteomics

Principal Investigator(s): Adam Resnick, Ph.D., Children’s Hospital of Philadelphia
Diagnosis/Classification: Supratentorial primitive neuroectodermal tumor and high-grade glioma
Project Summary: This project was a cohort for the expansion of CBTTC_0003 using Nanthealth. GPS platform for Whole Genome Sequencing, RNA sequencing and proteomics (FFPE) to validate using Nanthealth as a facility for Whole Genome Sequencing, RNA sequencing, and proteomics for future CBTTC projects.
Project Sponsor: Children’s Hospital of Philadelphia
Specimen Data: DNA, RNA, and slides from primary tumor specimens and blood-derived normal specimens for 2 supratentorial primitive neuroectodermal tumor patients and 4 high-grade glioma patients as part of CBTTC study cohort CBTTC_0007a.
Project Status: In-progress

Project 8: Developing a Novel Tumor Model to Screen for New Therapies for Spinal Ependymoma

Principal Investigator(s): Linda Resar, MD, The Johns Hopkins University School of Medicine; Li Luo, Ph.D., Johns Hopkins University Bloomberg School of Public Health; and Lingling Xian, MD, Ph.D., The Johns Hopkins University School of Medicine
Diagnosis/Classification: Ependymoma
Project Summary: This project aims to establish a unique tumor model and begin to identify new therapies for patients with ependymoma.
Project Sponsor: Alex’s Lemonade Stand Foundation (ALSF)
Specimen Data: Cell lines from 6 ependymoma patients will be generated and used as part of the CBTTC study cohort CBTTC_0008a.
Project Status: In-progress

Project 9: Neurocytoma WGS and RNAseq

Principal Investigator(s): Adam Resnick, Ph.D., Children’s Hospital of Philadelphia, Angela Waanders, MD, MPH, Children’s Hospital of Philadelphia
Diagnosis/Classification: Neurocytoma
Project Summary: For this project, tumors of the specific histologic diagnoses of Neurocytoma with or without matching blood specimens in the repository were identified for the whole-genome and RNA sequencing.
Project Sponsor:
Specimen Data: DNA and RNA from primary tumor specimens of 3 Neurocytoma patients and matched blood-derived normal specimens from two of those patients were used for data generation as part of the CBTTC study cohort CBTTC_0009a.
Project Status: In-progress

Project 10: Target Identification and Modeling of NF1-associated Low-grade Glioma

Principal Investigator(s): Michael Fisher, MD, Children’s Hospital of Philadelphia
Diagnosis/Classification: Low-grade gliomas
Project Summary: Synodos for NF1: This project aims at a comprehensive molecular and functional characterization of NF1-associated low-grade gliomas in children, to identify cooperating pathomechanisms with loss of NF1 and thereby potential new therapeutic vulnerabilities.
Project Sponsor: Children’s Tumor Foundation
Specimen Data: Primary tumor specimens from 13 NF-1 low-grade glioma patients and matched blood-derived normal specimens from 5 of those subjects were used for DNA and RNA extractions and will be sent for data generation as part of CBTTC study cohort CBTTC_0010a.
Project Status: In-progress

Project 11: Targeting Replicative Stress in Pediatric Brain Tumors with ALT

Principal Investigator(s): Kristina Cole, MD, Children’s Hospital of Philadelphia
Diagnosis/Classification: Supratentorial primitive neuroectodermal tumor and high-grade glioma
Project Summary: To screen tumor DNA for alternative lengthening of telomeres (ALT) to prioritize the development of ALT positive and ALT negative cell lines. The cell lines will be used to test inhibitors of replicative stress, to study downstream targeting, and to validate loss of function candidates of ALT inhibition.
Project Sponsor: Children’s Hospital of Philadelphia
Specimen Data: DNA from primary tumor specimens of 8 supratentorial primitive neuroectodermal tumor patients and 29 high-grade glioma patients will be used for data generation in this project. Cell lines from all these patients will also be generated. This data will be included as part of the CBTTC study cohort CBTTC_0011a.
Project Status: In-progress

Project 12: Pediatric Brain Tumor Atlas Initiative

Principal Investigator(s): Children’s Brain Tumor Tissue Consortium
Diagnosis/Classification: All tumor types in bank
Project Summary: CBTTC as a consortium has started an initiative to sequence the entire bank to generate genomic data. The specimens will be sequenced at NantHealth.  Whole Genome Sequencing (WGS) and RNA Sequencing (RNS Seq) will be conducted for all available specimens in the CBTTC biorepository.  The data extracted from these specimens will serve as a comparison for all future analyses performed within the CBTTC.
Project Sponsor: N/A
Specimen Data: Whole-genome sequencing and RNA sequencing for all available specimens in the bank
Project Status: In-progress

Project 13: Gene Expression Analysis Platform Evaluation for FFPE Specimen Material-Based Studies

Principal Investigator(s): Mateusz Koptyra, Ph.D., Children’s Hospital of Philadelphia; Adam Resnick, Ph.D., Children’s Hospital of Philadelphia
Diagnosis/Classification: Medulloblastoma, high-grade glioma, and supratentorial primitive neuroectodermal tumors
Project Summary: This project aims to validate a novel RNA analysis platform. FFPE tissue material will be processed by the HTG EdgeSeq technology pipeline for mRNA and/or miRNA profiling.
Project Sponsor: Internal funds – CHOP Center for Data-Driven Discovery in Biomedicine
Specimen Data: FFPE slides were created from primary tumor specimens from 6 Medulloblastoma patients, 4 high-grade glioma patients and 2 supratentorial primitive neuroectodermal tumor patients. This data will be generated as part of the CBTTC study cohort CBTTC_0013a.
Project Status: In-progress

Project 14: Evaluation of Immunosignature Profile in Medulloblastoma

Principal Investigator(s): Mateusz Koptyra, Ph.D., Children’s Hospital of Philadelphia; Adam Resnick, Ph.D., Children’s Hospital of Philadelphia; Dustin Hatefi, MD, MPH, UC San Diego Health System; Phillip Stafford, Ph.D., ASU Biodesign Institute; Stephen Johnston, Ph.D., ASU Biodesign Institute; Robert Wechsler-Reya, Ph.D., Sanford Burnham Prebys Medical Discovery Institute 
Diagnosis/Classification: Medulloblastoma
Project Summary: This project proposes to evaluate the immunosignature analysis pattern as a potential diagnostic tool in medulloblastoma patient’s stratification. We propose to analyze immunosignature profiles for medulloblastoma samples and compare them with the current subtype stratification consensus according to RNA profiling. Both analyses will be further compared to explore if and how immunosignature and RNA profiles overlap. We expect that our work will bring essential insights into the applicability of immunosignature assay in medulloblastoma tumor profiling and could potentially facilitate patients’ diagnostic and prognostic.
Project Sponsor: Arizona State University laboratory funding, Sanford Burnham Prebys Medical Discovery Institute laboratory funding
Specimen Data: 32 immunosignature assays from blood-derived normal specimens, 10 immunosignature assays from plasma-derived normal specimens, 35 microarray/RNA seq data analysis from primary tumor specimens
Project Status: In-progress

Project 15: Proteogenomic Identification of Structural Variations

Principal Investigator(s): Brian Rood, MD, Children’s National Health System; Javad Nazarian, Ph.D., MSC, Children’s National Health System
Diagnosis/Classification: Medulloblastoma
Project Summary: This project aims to discover novel genomic SVs encoding translated cancer-specific proteins with the potential for functional effects. Also to assay easily accessible ctDNA biomarkers. Tissue from 40 medulloblastoma patients will be used for data generation. From those 40 patients, DNA from flash-frozen tissue, plasma, and cerebral spinal fluid samples will be chosen for continued data generation. This data will be included as part of the CBTTC study cohort CBTTC_0015a.
Project Sponsor: Philanthropic Foundation Support
Specimen Data: Proteomic peptide sequencing, ddPCR
Project Status: In-progress

Project 16: Comprehensive Molecular Analysis of Pediatric Thalamic Tumors

Principal Investigator(s): Javad Nazarian, Ph.D., MSC, Children’s National Health System; Heloisa Moser, MD, Children’s National Health System
Diagnosis/Classification: Pediatric Thalamic Tumors
Project Summary: This project aims to generate the comprehensive molecular profile specific to primary thalamic tumors and to validate identified genomic aberrations in aim 1 using liquid biopsy (CSF) and WES (DNA from blood). Tissue and DNA from flash-frozen tissue from 52 patients, DNA from flash-frozen from an additional patient, plasma from 10 of the patients and CSF from 6 of the patients will be used for data generation. This data will be included as part of the CBTTC study cohort CBTTC_0016a.
Project Sponsor: Smashing Walnuts Foundation
Specimen Data: WES, RNAseq, proteomics, Genomic Liquid Biopsy
Project Status: In-progress

Project 17: Integrated Genomic Analysis to Elucidate the Role of the PIK3CA and 10q LOH as Unique Drivers and Cooperating Events in Pediatric High-grade Gliomas

Principal Investigator(s): Ian Pollack, MD, Children’s Hospital of Pittsburgh of UPMC; Sameer Agnihotri, Ph.D., Children’s Hospital of Pittsburgh of UPMC
Diagnosis/Classification: High-grade glioma, Brain Stem Glioma (DIPG)
Project Summary: This project aims to evaluate the frequency of PTEN loss/10q LOH and gain/activation of PIK3CA in pHGG, the clinical and molecular correlation associated with the PTEN/PIK3CA subgroup, and the integrated molecular analysis of the 10q LOH/PIK3CA subgroup. . DNA and RNA extracted from tissue from 126 high-grade glioma/DIPG patients will be used for data generation. From those patients, 56 DNA from blood and 6 cell lines will also be used for data generation. This data will be included as part of the CBTTC study cohort CBTTC_0017a.
Project Sponsor: R01 grant and start-up funds
Specimen Data: Targeted Gene Sequencing; Exome Sequencing; qPCR; RNAseq
Project Status: In-progress

Project 18: Development of the Ganglioside GD2 as a Biomarker and Clinical Trial Endpoint for Childhood Cancers

Principal Investigator(s): Frank Balis, MD, Children’s Hospital of Philadelphia; Christine Busch, Children’s Hospital of Philadelphia
Diagnosis/Classification: High-grade glioma, Medulloblastoma
Project Summary: This project aims to quantify serum GD2 concentrations in patients with a variety of common childhood cancers, including brain tumors, and in children without cancer to assess the specificity of GD2 as a tumor biomarker for neuroblastoma and other neuronal tumors. Plasma from 8 high-grade glioma patients and 8 medulloblastoma patients will be used for data generation. This data will be included as part of the CBTTC study cohort CBTTC_0018a.
Project Sponsor: COGSM-ITSC Grant
Specimen Data: Biomarker Assay
Project Status: In-progress

 Project 19: Integrative Functional Genomics of Recurrent Childhood Medulloblastoma

Principal Investigator(s): Javad Nazarian, Ph.D., MSC, Children’s National Health System; Brian Rood, MD, Children’s National Health System; Paul Northcott, Ph.D., St. Jude Children’s Research Hospital
Diagnosis/Classification: Medulloblastoma
Project Summary: This project aims to assess the conservation and divergence of already generated (CBTTC) genomic and transcriptional landscapes in patient-matched primary/relapse medulloblastoma pairs, assess methylation profiles in patient-matched primary/relapse medulloblastoma pairs and functionally validate and therapeutically target molecular events enriched at medulloblastoma relapse. DNA extracted from tissue from 22 medulloblastoma patients will be used for data generation. This data will be included as part of the CBTTC study cohort CBTTC_0019a.
Project Sponsor:
Specimen Data: Methylation Array Data
Project Status: In Progress

Project 20: Choroid Plexus Tumor (CPT) Therapies Based on Patient-Derived Cell Culture Resources

Principal Investigator(s): Mark Souweidane, MD, Weill Cornell Brain and Spine Center, Uday Bhanu Maachani, Ph.D., Weill Cornell Brain and Spine Center
Diagnosis/Classification: Choroid Plexus Carcinoma
Project Summary: This project aims to establish cell lines from a choroid plexus carcinoma sample to understand the molecular etiology of these cell lines in vitro and in vivo animal xenograft models to design effective therapies. The tissue in freezing media from one choroid plexus carcinoma patient will be used for cell line generation.
Project Sponsor: Souweidane Lab
Specimen Data: Cell Line Generation
Project Status: In Progress

Project 22: Beijing Genomics Institute (BGI) Validation Cohort

Principal Investigator(s): Adam Resnick, Ph.D., Children’s Hospital of Philadelphia;  Marilyn Li, MD, Children’s Hospital of Philadelphia
Diagnosis/Classification: Low-grade glioma/astrocytoma, craniopharyngioma, Supratentorial or Spinal Cord PNET, medulloblastoma, high-grade glioma/astrocytoma
Project Summary: This project aims to validate an additional sequencing platform for future CBTTC data generation DNA extracted from tissue from one medulloblastoma patient and one supratentorial or spinal cord PNET patient; DNA extracted from blood from two low-grade glioma patients and one craniopharyngioma patient; and RNA extracted from tissue from one medulloblastoma patient, one supratentorial or spinal cord PNET patient and four high-grade glioma patients will be used for data generation. This data will be included as part of the CBTTC study cohort CBTTC_0022a.
Project Sponsor: Beijing Genomics Institute (BGI)
Specimen Data: Whole Genome Sequencing, RNA sequencing
Project Status: In Progress

Project 23: Kids First – CBTTC Proteogenomic Pilot Project

Principal Investigator(s): Adam Resnick, Ph.D., Children’s Hospital of Philadelphia; Brian Rood, MD, Children’s National Medical Center
Diagnosis/Classification: All pediatric brain tumor histologies
Project Summary: This project aims to perform comprehensive quantitative and associated post-translational analyses on a pilot cohort of pediatric brain tumors. This data will be included as part of the CBTTC study cohort CBTTC_0023a.
Project Sponsor: NIH RAS Program
Specimen Data: Proteomics
Project Status: In-progress

Project 25: Development of Preclinical Models of Pediatric Ependymoma

Principal Investigator Names: Dr. Ching C. Lau
Diagnosis/Classification: Ependymoma
Project Summary:
This project aims to develop patient-derived orthotopic xenograft models, 2D and 3D cultures, in order to study the biology of these tumors and also preclinical drug screening.
Project Sponsor:
Internal funding at Jackson Lab
Specimen Data:
N/A
Project Status:
In Progress

Project 27: Cracking the Histone Code: Characterizing Pediatric Brain Tumor Epigenetics Using Cerebrospinal Fluid

Principal Investigator(s): Amanda Saratsis, MD, Ann & Robert H. Lurie Children’s Hospital of Chicago; Rishi Lulla, MD, Ann & Robert H. Lurie Children’s Hospital of Chicago
Diagnosis/Classification: High-grade gliomas and DIPG
Project Summary: This project aims to characterize protein expression and Histone H3 post-translational modifications in pediatric brain tumors and characterize tumor transcriptomes with respect to histone H3 post-translational modifications. This data will be included as part of the CBTTC study cohort CBTTC_0027a.
Project Sponsor: Institutional Funding and foundation support; CBTTC Advisory Council Research Award
Specimen Data: Proteomics
Project Status: In Progress

Project 28: GPC2 As an Immunotherapeutic Target in Medulloblastoma and Other Pediatric Brain Tumors

Principal Investigator(s): Jessica Foster, MD, Children’s Hospital of Philadelphia; Kristopher Bosse, MD, Children’s Hospital of Philadelphia
Diagnosis/Classification: ATRT, High-Grade gliomas, and medulloblastoma
Project Summary: This project aims to perform a pan-pediatric brain tumor assessment for high GPC2 expression and define the efficacy of the GPC2 ADC D3-GPC2-PBD in medulloblastoma preclinical models. This data will be included as part of the CBTTC study cohort CBTTC_0028a.
Project Sponsor: ALSF, HHOW, Damon Runyon Foundation; CBTTC Advisory Council Research Award
Specimen Data: Cell lines will be generated
Project Status: In Progress

Project 29: Molecular Analysis of the Cellular Ecosystem of Childhood Ependymoma

Principal Investigator(s): Pablo Gonzalez Camara, Ph.D., University of Pennsylvania
Diagnosis/Classification: Ependymoma
Project Summary: This project aims to use single-nuclei RNA-sequencing of flash-frozen specimens and immunohistochemistry staining of cryosections from the same specimens to infer the composition and evolution of the tumor microenvironment in relation to the tumor progression. The results of this study will be used to pinpoint the molecular mechanisms of ependymoma progression and to identify consequent potential targets for immunotherapeutic intervention. This data will be included as part of the CBTTC study cohort CBTTC_0029a.
Project Sponsor: Departmental Funds; CBTTC Advisory Council Research Award
Specimen Data: Single Nuclei RNA-sequencing
Project Status: In Progress

Project 30: Interactions between astrocytes and tumor cells are critical for medulloblastoma growth

Principal Investigator Names: Zeng-jie Yang, MD, Ph.D., Fox Chase Cancer Center
Diagnosis/Classification: Medulloblastoma
Project Summary:
This project aims to examine the mutual support of astrocytes and tumor cells purified from human MB, by a co-culture method or intracranial transplantation and investigate the alterations of gene/protein expression in tumor cells and astrocytes after being co-cultured or cultured alone by RNA sequencing or MS-Spec. The results of this study will be used to shed light on the important functions of tumor microenvironment in MB tumorigenesis, also demonstrate tumor microenvironment as a promising therapeutic target for MB treatment.
Project Sponsor:
NCI and ACS; CBTTC Advisory Council Research Award
Specimen Data:
N/A
Project Status:
In Progress

Project 33: Center for Pediatric Tumor Cell Atlas

Principal Investigator Names: Kristina Cole, MD, Ph.D., Children’s Hospital of Philadelphia
Diagnosis/Classification: High-grade Glioma
Project Summary: 
The goal of the Center for Pediatric Tumor Cell Atlas (CPTCA) is to molecularly characterize the genome, transcriptome, methylome and chromatin accessibility at critical transition points for pediatric high-grade gliomas (and other pediatric cancers).
Importance of CBTTC for this research: 
Our existing biorepository infrastructure is modern, streamlined and highly supported. Our leadership role in several similar, large scale multi-institutional projects have changed the therapeutic approach and standard of care of specific pediatric cancers and provide further evidence that the structure is already in place to ensure the success of this proposed Atlas.
Impact of Project: 
Relapsed pediatric high-grade glioma, high-risk neuroblastoma and VHR-ALL account for more than half of all pediatric cancer deaths. In order to advance novel therapies for children with these tumors, there is a need to fully genomically characterize and query the tumor’s responses to therapy and the development of therapy resistance with both spatial and temporal single-cell resolution. Our established biorepository and historical commitment to both resource and data sharing guarantee that the entire research and patient community will benefit.
Project Sponsor: 
NIH-U2CCA233285; CBTTC Advisory Council Research Award
Specimen Data: 
Single Cell Sequencing
Project Status: 
In Progress

Project 34: Pediatric brain tumor miRNA profiling for the cohort of Children’s Brain Tumor Tissue Consortium specimens

Principal Investigator Names: Mateusz Koptyra, Ph.D., Children’s Hospital of Philadelphia
Diagnosis/Classification: All brain tumor types
Project Summary: 
This project aims to perform miRNA panel analysis using the HTG EdgeSeq miRNA panel analysis. The data will be immediately returned to the Operations Center to be deposited into Cavatica for “no embargo” access and utilization in approved research explorations. 
Importance of CBTTC for this research: 
Recent efforts from Children’s Brain Tumor Tissue Consortium (CBTTC), Cavatica, Kids First effort, and D3b center led to the creation of one of the world’s most comprehensive collections of childhood brain tumor data. The data is now available to researchers as the Pediatric Brain Tumor Atlas (PBTA), an initiative seeking to transform the discovery process and accelerate the translation of large-scale molecular and clinical datasets to novel therapeutic approaches for children affected by brain tumors. The first cohort of PBTA sample subset (utilized in CBTTC Project 23) which consists of tumor and germline whole-genome sequencing, RNAseq and proteomic (targeted and phosphor –proteomic) profiling provides the unique opportunity expand the data set with the introduction of miRNA analysis.
Impact of Project: 
The project will support the CBTTC vision of open access and collaboration by generating a significant amount of free data for further analysis by researchers worldwide, both within and outside of the consortium.
Project Sponsor: 
D3b center internal funding / HTG Molecular Diagnostics; CBTTC Advisory Council Research Award
Specimen Data: 
miRNA sequencing
Project Status:
In Progress

Project 35: Elucidating the somatic epigenetic landscape of pediatric meningioma and schwannoma

Principal Investigator Names: Sameer Agnihotri, Ph.D., UPMC Children’s Hospital of Pittsburgh
Diagnosis/Classification: Meningioma and Schwannoma
Project Summary: 
This project aims to determine the epigenetic landscape of pediatric meningiomas and schwannomas, determine the global copy number alterations in pediatric meningioma and schwannomas and Compare the epigenetic and copy number landscape of these tumors to their adult counterparts.  
Importance of CBTTC for this research: 
Accessing the CBTTC samples will allow an unprecedented epigenetic analysis of pediatric meningiomas. and schwannomas. Using integrative methylation profiling we will conclusively address how pediatric meningiomas and schwannomas are both similar or unique from their adult counterparts. This project can only be completed with the use of CBTTC samples.
Impact of Project: 
The methylation profiles of pediatric meningioma and schwannomas with clinical annotation will allow for a comprehensive analysis of pediatric meningiomas and may identify novel targeted therapies or predict which patients may be susceptible to local recurrence.
Project Sponsor: 
Agnihotri lab start-up funds, Aldape Lab; Advisory Council Research Award
Specimen Data: 
Methylation analysis
Project Status: 
In Progress

Project 37: Project HOPE: “High-Grade Glioma-Omics in Pediatric and AYA”

Principal Investigator Names: Adam Resnick, Ph.D., Children’s Hospital of Philadelphia
Diagnosis/Classification: High-Grade Glioma
Project Summary: 
The goals of Project Hope are to perform single-cell sequencing of cancer cells and tumor-infiltrating immune cells; Single nucleus sequencing of the non-immune microenvironment in pediatric and AYA high-grade gliomas and data sharing.
Importance of CBTTC for this research: 
The goals of Project Hope are to perform single-cell sequencing of cancer cells and tumor-infiltrating immune cells; Single nucleus sequencing of the non-immune microenvironment in pediatric and AYA high-grade gliomas and data sharing.
Impact of Project: 
Archival tissue and those obtained from prospective trials provide an exciting opportunity for more complex and deeper molecular and immunologic investigations.
Project Sponsor: A focus on single-cell techniques, the microenvironment, and the immunologic status of tumors and matched preclinical models will lead to a better understanding of these diseases and the development of more effective therapeutics to improve outcomes for patients.
Specimen Data: Methylation analysis
Project Status: 
In Progress

Project 38: Germline and Somatic Determinants of Paediatric Brain Tumor Evolution

Principal Investigator Names: Sorana Morrisy, Ph.D., University of Calgary; Marco Gallo, Ph.D., University of Calgary
Diagnosis/Classification: High-grade Glioma
Project Summary: 
CBTTC samples will be used to increase a cohort of pediatric brain tumors for genomic analysis and functional studies
Importance of CBTTC for this research: 
Without access to CBTTC samples, this study would have been severely underpowered and limited in its ability to understand 
Impact of Project: 
To understand and analyze the tumor mutation caused by the extreme evolution of high-grade gliomas, including GBM’s and other tumors
Project Sponsor: Morrisy & Gallo grants; startup funding
Specimen Data:
Project Status: 
In Progress

Project 39: Clinical, Radiologic, and Molecular Characteristics of Anaplastic Pleomorphic Xanthoastrocytomas

Principal Investigator Names: Alberto Broniscer, MD, MS, UPMC Children’s Hospital of Pittsburgh
Diagnosis/Classification: Pleomorphic Xanthoastrocytomas (PXAs)
Project Summary: 
We hope to increase the number of cases and tumor/germline samples available for analyses by including cases obtained from Children’s Brain Tumor Tissue Consortium (CBTTC). We hope to obtain clinical and radiologic information from CBTTC about potential cases of anaplastic PXAs, if available. We hope to get either data already analyzed, if available (e.g., whole-exome and RNA sequencing) or DNA to perform methylation array studies in available samples.
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In Progress

Project 40: CRISPR Targeting of Metabolic Pathways in Gliomas

Principal Investigator Names: Nicholas Ahye, MD, Temple University
Diagnosis/Classification: Gliomas
Project Summary: 
Glioma cell lines will be cultured and transfected with CRISPR constructs targeting the glutamine synthetase enzymes. Cell viability and metabolic activity assays will then be performed. 
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In Progress

Project 41: Central Nervous System Cancers in Patients with Non-Neurofibromatosis

Principal Investigator Names: Alberto Broniscer, MD, MS, UPMC Children’s Hospital of Pittsburgh
Diagnosis/Classification: (NF-1) RASopathies
Project Summary: 
 We are collecting cases of the association of non-NF-1 RASopathies and CNS cancers at our institution and from other institutions in the US. By using data from cases collected through CBTTC, we are hoping to increase the size of our cohort of research participants.
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In Progress

Project 42: Maternal Microchimerism in Human Brain

Principal Investigator Names: J. Lee Nelson, MD, Fred Hutchinson Cancer Research Center
Diagnosis/Classification: Not specified
Project Summary: 
We will use the data generated from CBTTC specimens as a comparison to similar studies that we have completed for patients who underwent excision for medication refractory epilepsy.
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In Progress

Project 43: Oncolytic Virus to Potentiate Immune-Checkpoint Blockade in Immunologically Cold Pediatric Brain Tumors

Principal Investigator Names: Aaron Diaz, Ph.D., University of California San Francisco
Diagnosis/Classification: Medulloblastoma, ATRT
Project Summary: 
Frozen tissue is requested for single-cell RNA sequencing. FFPE tissue is requested for bulk RNA sequencing.
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In Progress

Project 45: Molecular and Functional Characterization of Childhood Supratentorial Ependymoma

Principal Investigator Names: Vijay Ramaswamy, MD, Ph.D., The Hospital for Sick Children
Diagnosis/Classification: Ependymoma
Project Summary: 
CBTTC clinical and specimen data will be used to extend findings I have generated in a discovery cohort pertaining to the genomic landscape of pediatric supratentorial ependymoma, and the nature of fusions found in the RELA methylation group.
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In Progress

Project 46: Genomic Analysis of Oligodendrogliomas Across Pediatrics, Adolescents, and Adults

Principal Investigator Names: Adam Resnick, Ph.D., Assistant Professor of Neurosurgery at Children’s Hospital of Philadelphia
Diagnosis/Classification: Oligodendrogliomas
Project Summary: 
This project will generate WGS and RNAseq data to research use statement (3 sentences MAX) perform genomic analysis oligodendrogliomas across pediatrics, adolescents, and adults.
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In Progress

Project 47: Elucidating the Role of Driver Mutations in Pediatric High-Grade Glioma

Principal Investigator Names: Thomas De Raedt, Ph.D., Children’s Hospital of Philadelphia
Diagnosis/Classification: High-Grade Glioma
Project Summary: 
Cell lines: We will knock down or overexpress specific genes and assess proliferation, changes in gene expression and changes in the epigenome. Tumor and cell line TMA: we will stain samples using CYCIF (cyclic IF) and overlay imaging data with mutation data from the samples.
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In Progress

Project 48: Disclosing Chromatin Accessibility in Brain Tumor Cells after Treatment by Cracking a ‘Nucleosomal Code’

Principal Investigator Names: Jakub Mieczkowski, Ph.D., Nencki Institute of Experimental Biology Polish Academy of Sciences and Katarzyna Leszczynska, Ph.D., Nencki Institute of Experimental Biology Polish Academy of Sciences
Diagnosis/Classification: High-Grade Glioma
Project Summary: 
Once we will observe the effect in the epigenetic drug treatments on the chromatin accessibility in HGG cell lines, we would like to use the CBTTC data available for these cell lines to compare the information with our own data and to see if this can help us to guide us in the later stages of the project/mechanistic experiments or validation.
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In Progress

Project 49: CBTTC Cell Lines High Throughput Drug Screening Study

Principal Investigator Names: Adam Resnick, Ph.D., Children’s Hospital of Philadelphia and Mateusz Koptyra, Ph.D., Children’s Hospital of Philadelphia
Diagnosis/Classification: All
Project Summary: 
The cell lines will be utilized in the high throughput approach in-vitro drug testing. This project will provide extensive in-vitro drug response information across multiple pediatric tumor diagnoses providing the pediatric brain tumor cell line drug response atlas. 
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In Progress

Project 50: Elucidate Potential Therapeutic Targets in H3.3G34 Mutant pHGG Cells

Principal Investigator Names: Zhiguo Zhang, Ph.D., Columbia University
Diagnosis/Classification: High-Grade Glioma
Project Summary: 
The cell lines will be used for cell viability assays, CRISPR/Cas9 screen as well as other assays for basic research.
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In Progress

Project 53: Circular RNAs in Medulloblastoma

Principal Investigator Names: Peter George Zaphiropoulos, Ph.D., Karolinska Institutet, Sweden
Diagnosis/Classification: Medulloblastoma
Project Summary: 
We would like eight medulloblastoma RNA samples, preferably of the SHH subgroup. We will perform RNAseq tailored to detect circular RNAs as well as standard RNAseq. We anticipate that this works will help in dissecting the functions of circular RNA expression in medulloblastoma development.
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In Progress

Project 54: Genetic Susceptibility to Medulloblastoma

Principal Investigator Names: Maral Adel Fahmideh, Ph.D., Baylor College of Medicine
Diagnosis/Classification: Not specified
Project Summary: 
In this study, we aim to identify genetic markers that play an important role in the increased risk of childhood brain tumors.
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In Progress

Project 55: Using Whole-Genome Bisulfite Sequencing to Identify Novel Therapeutic Targets in DIPG and ATRT

Principal Investigator Names: Eric Raabe, MD, Ph.D., Johns Hopkins Division of Pediatric Oncology and Michael Koldobskiy, MD, MS, Ph.D., Johns Hopkins Medicine
Diagnosis/Classification: DIPG and ATRT
Project Summary: 
We will perform whole-genome bisulfite sequencing (wgbs) on DIPG and ATRT and analyze using novel computational techniques pioneered in the Fineberg/Koldobsky lab to identify regions of the genome with high degrees of variation. These regions are correlated with dependence on key genes. We will validate targets in our 8 human DIPG cell lines and using RNA seq data already extant in CBTTC. Findings will be incorporated into the PNOC DMG ACT pre-clinical testing consortium.
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In Progress

Project 56: Defining the Role of the Histone 3 (H3.3G34R) Mutation in the Pathogenesis of Pediatric High Astrocytoma

Principal Investigator Names: Cynthia Hawkins, MD, Ph.D., The Hospital for Sick Children
Diagnosis/Classification: Not specified
Project Summary: 
The patient-derived cell lines will be used to validate the findings from our preliminary experiments. They will be essential in that they endogenously express the H3.3G34R mutant line. Further, they will be critical for determining the clinical significance of our findings and for testing potential novel therapeutic approaches.
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In Progress

Project 57: The Role of Genetic Factors in Ependymoma Susceptibility

Principal Investigator Names: Maral Adel Fahmideh, Ph.D., Baylor College of Medicine
Diagnosis/Classification: Not specified
Project Summary: 
In this study, we aim to identify genetic markers that play an important role in the increased risk of childhood brain tumors.
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In Progress

Project 58: Genomic Analysis of Chordomas Across the Pediatrics, Adolescents, and Adults

Principal Investigator Names: Adam Resnick, Ph.D., Assistant Professor of Neurosurgery at Children’s Hospital of Philadelphia and Stephanie Stefankiewcz, Children’s Hospital of Philadelphia
Diagnosis/Classification: Chordoma
Project Summary: 
All data generated from this cohort will be uploaded to Cavatica and made available through the Kids First Data Resource Portal.
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In Progress

Project 59: Identification of Circulating Noncoding RNAs and Metabolites in Cerebrospinal Fluid (CSF) in Medulloblastoma Patients

Principal Investigator Names: Ranjan J. Perera, Ph.D., Johns Hopkins University School of Medicine—All Children’s Hospital
Diagnosis/Classification: Medulloblastoma
Project Summary: 
Identification IncRNA and metabolites and medulloblastoma group-specific biomarkers.
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In Progress

Project 60: Therapeutic Targetting of the Blood-Brain Barrier in Pediatric Malignant Brain Tumors

Principal Investigator Names: Sadhana Jackson, MD, National Institutes of Health (NIH)
Diagnosis/Classification: Malignant Gliomas
Project Summary: 
Our studies are focused on understanding why drugs have a hard time getting to brain tumor cells. The wall known as the blood-brain barrier allows drugs to pass in certain areas but not in other areas. We want to understand more about the restricted areas.
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In Progress

Project 61: Targeting Medulloblastoma by Regulating RNA Binding Proteins

Principal Investigator Names: Robert Schnepp, MD, Ph.D., Emory University and Shubin Shahab, MD, Ph.D., Emory University
Diagnosis/Classification: Medulloblastoma
Project Summary: 
Profiling protein and RNA expression; functional assays to knock down or overexpress gene expression.
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In Progress

Project 62: Investigating the Metabolic Hallmarks of Oligodendroglioma

Principal Investigator Names: Samuel McBrayer, Ph.D., University of Texas Southwestern Medical Center
Diagnosis/Classification: Oligodendroglioma
Project Summary: 
We propose to create a metabolic atlas of oligodendroglioma featuring samples incorporated from the CBTTC. This study will provide additional ‘omics’-level data for this disease that will complement existing genomics and transcriptomics datasets. We will collaborate with Dr. Adam Resnick to integrate our metabolomics data produced by analyzing CBTTC samples into pediatric glioma databases.
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In Progress

Project 66: Impeding LIN28 Function in ATRT

Principal Investigator Names: Giselle Saulnier Sholler, MD, Helen DeVos Children’s Hospital
Diagnosis/Classification: Not specified
Project Summary: 
We hypothesize that pharmacological targeting of the LIN28 pathway with DFMO will suppress growth, proliferation, and decrease tumor initiation in ATRT. We aim to determine if pharmacological treatment of ATRT cell lines with DFMO results in reductions in viability, tumor initiation, and LIN28 protein levels. We will test a series of doses of DFMO to assess the effects on ATRT cell viability, proliferation rates, tumor initiation, and proteins of interest including LIN28. We also aim to ascertain if DFMO induced effects in ATRT are pan disease or subtype-specific. We will use a collection of ATRT cell lines with disparate molecular phenotypes and subgrouping to determine if treatment with DFMO produces similar results within a heterogeneous group of samples.
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In Progress

Project 68: DNA Methylation Signatures of Cell-Free DNA in CSF as a New Response Biomarker for Pediatric Medulloblastoma

Principal Investigator Names: Deqiang Sun, Ph.D., Texas A&M University
Diagnosis/Classification: Medulloblastoma
Project Summary: 
We will perform WGBS on applied de-identified MB tumor tissue samples. Methylome generated by our uniform analysis pipeline will extend our own sample database. The collected data will be used as a reference to identify MB specific markers in CSF methylome. The more data we collect, the more confidence we will have on MB specific markers from CSF, which will yield better prediction results for clinical usage.
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In Progress

Project 69: Delineating Pediatric Glioma Progression Under Single-Nuclei Sequencing

Principal Investigator Names: Trevor Pugh, Ph.D., University Health Network and Arash Nabbi, Ph.D., University Health Network
Diagnosis/Classification: Not specified
Project Summary: 
Brain cancer are devestating diseases in children with few treatment options currently available. We will study how brain tumors shape over time in children by looking at changes in genes in tumor biopsies. We will then nominate potential drug targets that can delay the tumor comeback.
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In Progress