Scientific Projects

Scientific Projects

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.
Scientific proposals can be submitted at any time and are evaluated as soon as they are received.  The current time from approved scientific proposal to release of specimens by the CBTTC Operations Center is less than one month and is expected to be even faster once a new automated request system is launched in 2016.

This process includes a review of the project proposal by the scientific committee along with a detailed report of the specimens being requested. 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, 150 whole genomes, 200 RNA profiles and 50 whole exomes 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, please click the button below

Submit a Scientific Project


CBTTC Scientific Projects

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
Contact: resnick@email.chop.edu
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 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
Contact: resnick@email.chop.edu
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 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, PhD, FRCP(C), Toronto Hospital for Sick Children
Contact: sarah.leary@seattlechildrens.org; waandersa@email.chop.edu; annie.huang@sickkids.ca
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, PhD, Children’s Hospital of Philadelphia (PEDSNet), Xiaohua Tony Hu, PhD, Drexel University
Contact: felmeistera@email.chop.edu
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 facility 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)
Contact:
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 CBTTC study cohort CBTTC_0004d and made available in April 2016. These data were generated as part of 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,PhD, Northwestern University Feinberg School of Medicine; Craig M. Horbinski, MD, PhD, Northwestern University Feinberg School of Medicine
Contact: rlulla@luriechildrens.org; derekwainwright@northwestern.edu; craig.horbinski@northwestern.edu
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 PhD, Weill Cornell Brain and Spine Center; Jeff Greenfield, MD, PhD, Weill Cornell Brain and Spine Center
Contact: shl2018@med.cornell.edu; jpgreenf@med.cornell.edu
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, PhD, Children’s Hospital of Philadelphia
Contact: resnick@email.chop.edu
Diagnosis/Classification: Supratentorial primitive neuroectodermal tumor and high grade glioma
Project Summary: This project was a cohort for 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 specimsn 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, PhD, Johns Hopkins University Bloomberg School of Public Health; and Lingling Xian, MD, PhD, The Johns Hopkins University School of Medicine
Contact: lresar@jhmi.edu; li.luo@jhmi.edu;
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 CBTTC study cohort CBTTC_0008a.
Project Status: In-progress

Project 9: Neurocytoma WGS and RNAseq

Principal Investigator(s): Adam Resnick, PhD, Children’s Hospital of Philadelphia, Angela Waanders, MD, MPH, Children’s Hospital of Philadelphia
Contact: resnick@email.chop.edu; waandersa@email.chop.edu
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 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 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
Contact: fisherm@email.chop.edu
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
Contact: colek@email.chop.edu
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 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
Contact: CBTTCadmin@email.chop.edu
Diagnosis/Classification: All tumor types in bank
Project Summary: The CBTTC has partnered with Children’s Hospital of Orange County 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, PhD, Children’s Hospital of Philadelphia; Adam Resnick, PhD, Children’s Hospital of Philadelphia
Contact: koptyram@email.chop.edu; resnick@email.chop.edu
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 CBTTC study cohort CBTTC_0013a.
Project Status: In-progress

Project 14: Evaluation of Immunosignature Profile in Medulloblastoma

Principal Investigator(s): Mateusz Koptyra, PhD, Children’s Hospital of Philadelphia; Adam Resnick, PhD, Children’s Hospital of Philadelphia; Dustin Hatefi, MD, MPH, UC San Diego Health System; Phillip Stafford, PhD, ASU Biodesign Institute; Stephen Johnston, PhD, ASU Biodesign Institute; Robert Wechsler-Reya, PhD, Sanford Burnham Prebys Medical Discovery Institute
Contact: koptyram@email.chop.edu; resnick@email.chop.eduphillip.stafford@asu.edustephen.johnston@asu.edurwreya@SBPdiscovery.org 
Diagnosis/Classification: Medulloblastoma
Project Summary: This project proposes to evaluate immunosignature analysis pattern as a potential diagnostic tool in the medulloblastoma patient’s stratification. We propose to analyze immunosignature profiles for medulloblastoma samples and compare them with current subtype stratification consensus according to RNA profiling. Both analysis will be further compared to explore if and how immunosignature and RNA profiles overlap. We expect that our work will bring essential insights into 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, PhD, MSC, Children’s National Health System
Contact: brood@cnmc.org; jnazarian@childrensnational.org 
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 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, PhD, MSC, Children’s National Health System; Heloisa Moser, MD, Children’s National Health System
Contact: jnazarian@childrensnational.orghmoser@childrensnational.org
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 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, PhD, Children’s Hospital of Pittsburgh of UPMC
Contact: pollaci@upmc.edu; sameer.agnihotri@gmail.com
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 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
Contact: balisf@email.chop.edu; buschc@email.chop.edu
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 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 Names: Javad Nazarian, PhD, MSC, Children’s National Health System; Brian Rood, MD, Children’s National Health System; Paul Northcott, PhD, St. Jude Children’s Research Hospital
Contact: JNazarian@childrensnational.org; BRood@childrensnational.org; paul.northcott@stjude.org
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 CBTTC study cohort CBTTC_0019a.
Project Sponsor:
Specimen Data: Methylation Array Data
Project Status: In Progress