2016-17 Annual Report


Children’s Brain Tumor Tissue Consortium Annual Report 2016-17

About the CBTTC

The Children’s Brain Tumor Tissue Consortium (CBTTC) is a collaborative, multi-institutional research program dedicated to the study and treatment of childhood brain tumors. The CBTTC supports the research of new prognostic biomarkers and therapies for the effective treatment of children with brain tumors. As part of this research effort, the CBTTC has developed a network of informatics and data applications which allow researchers from across the world to work together to discover cures. “Innovation through collaboration” is made possible by the CBTTC’s state-of-the-art biorepository as well as expertise of leaders in the field of biomedicine.

The CBTTC consists of 15 national and international primary member institutions including:

CBTTC Infographic

1) Children’s Hospital of Philadelphia (CHOP), 2) Children’s Hospital of Pittsburgh of UPMC, 3) Seattle Children’s Hospital, 4) Ann & Robert H. Lurie Children’s Hospital of Chicago, 5) Meyer Children’s Hospital (Florence, Italy), 6) UCSF Benioff Children’s Hospital, 7) Lucile Packard Children’s Hospital Stanford, 8) Bristol-Meyers Squibb Children’s Hospital at Robert Wood Johnson University Hospital, 9) Children’s National Health System, 10) Weill Cornell Pediatric Brain & Spine Center, 11) Joseph M. Sanzari Children’s Hospital at Hackensack University Medical Center, 12) Children’s Hospital of Orange County: CHOC Children’s, 13) University of California Santa Cruz: Treehouse Childhood Cancer Initiative, 14) The Beijing Tiantan Hospital Neurosurgery Center (Beijing, China), and 15) China National Genebank (Beijing Genomics Institute – Shenzhen, China).

The operations center of the CBTTC is located at Children’s Hospital of Philadelphia and integrates genomic and molecular research, biorepository management, and support for the informatics platforms of the CBTTC. This infrastructure serves an important role in the CBTTC’s ability to provide free and open access to brain tumor data to researchers throughout the world.

Message from Rishi Lulla, MD, MS, Chair of the Executive Board

Rishi R. Lulla, MD, MS was appointed as Chair of the Executive Board of the Children’s Brain Tumor Tissue Consortium in August of 2016. He is an attending physician of Hematology, Oncology, Neuro-Oncology & Stem Cell Transplantation at Ann & Robert H. Lurie Children’s Hospital of Chicago and Associate Professor of Pediatrics at the Northwestern University Feinberg School of Medicine.

Dear CBTTC Colleagues and Supporters,

It is with great pride that we present the 2016-2017 CBTTC Annual Report. I’ve had the privilege of serving as the CBTTC Executive Board Chair since last August and am energized by our accomplishments during this transformational year.

The CBTTC is in a phase of exponential growth and this year the consortium expanded to include a total of 15 member institutions across the globe. We continue to experience growth in the number of patient samples and corresponding clinical and genomic data in our biobank. We are proud to be the largest, clinically annotated pediatric brain tumor database in the world. Our platform has been further strengthened by the launch of CAVATICA. We are now able to store, share, and analyze genomic data sets in a more powerful
way than ever before through accelerating discovery with the world’s research community. One of the consortium’s overarching goals is to empower research projects, and this year was no different, with eight new scientific projects reviewed and approved.

We are working hard to increase the visibility and branding of CBTTC in the scientific and fundraising communities, and this year we were invited to present at six national meetings to share our platform and other CBTTC projects. A manuscript describing our unique infrastructure for research will be submitted in the coming weeks.

Earlier this year, we launched the CBTTC Advisory Council — a group of 14 like-minded, family foundations who have committed effort and/or financial resources to the development and growth of the CBTTC. Under the leadership of Allen Gustafson of the Swifty Foundation, the Council will advise us with regard to strategic initiatives and consortium sustainability. We remain deeply grateful to the over 40 partner foundations who have contributed generously to the CBTTC as it would not exist without their support.

I want to take a moment to offer special thanks to our CBTTC colleagues at all the member and satellite sites for their invaluable contributions to the project. I’m personally grateful for their support of the leadership changes this year. Our accomplishments would not have been possible without the partnership of Drs. Adam Resnick and Javad Nazarian who chair the Scientific Committee. And finally, the CBTTC thrives because of the dedication and hard work of Dr. Angela Waanders, Jennifer Mason and the entire team at the Operations Center – we could not do it without you.

For the year ahead, we have an ambitious list of objectives focused on improving our operations center processes, increasing our scientific productivity and supporting the growth and sustainability of the CBTTC. I very much look forward to sharing our progress again with you next year.

With best wishes,

Rishi R. Lulla MD, MS

CBTTC Member Institutions

member institutions

Children’s Hospital of Philadelphia (CHOP)

Children’s Hospital of Pittsburgh of UPMC

Seattle Children’s Hospital

Ann & Robert H. Lurie Children’s Hospital of Chicago

Meyer Children’s Hospital (Florence, Italy)

UCSF Benioff Children’s Hospital

Lucile Packard Children’s Hospital Stanford

Bristol-Meyers Squibb Children’s Hospital at Robert Wood Johnson University Hospital

Children’s National Health System

Weill Cornell Pediatric Brain & Spine Center

Joseph M. Sanzari Children’s Hospital at Hackensack University Medical Center

Children’s Hospital of Orange County: CHOC Children’s

University of California Santa Cruz: Treehouse Childhood Cancer Initiative

The Beijing Tiantan Hospital Neurosurgery Center (Beijing, China)

China National Genebank (Beijing Genomics Institute – Shenzhen, China)


Message from Adam Resnick, PhD & Javad Nazarian, PhD

Co-Chairs of the Scientific Committee

Adam Resnick, PhD, is the Director of Data Driven Discovery in Biomedicine (D3b) at Children’s Hospital of Philadelphia (CHOP). Dr. Resnick serves as Scientific Chair for several consortia-based efforts, including the Children’s Brain Tumor Tissue Consortium (CBTTC) and Pacific Pediatric Neuro-Oncology Consortium (PNOC), which include more than 20 pediatric hospitals across the globe.

Javad Nazarian, PhD, is an investigator at the Center for Genetic Medicine at Children’s National Medical Center in Washington D.C., an associate professor of Pediatrics and Integrative Systems Biology at George Washington University, and the Scientific Director of the Brain Tumor Institute at Children’s National Health System.

This year has been a sucessful year of growth and expansion for biobanking, large-scale data generation, the expansion of collaborative efforts, raising national awareness, and securing research funding in pursuit of our mission to accelerate discovery and effectively treat childhood brain tumors. This past year’s enrollment of new institutions in our consortium, and the associated expansion of the number of banked biospecimens and consortium-based projects indicates and further ensures that we are on the right path to discover new prognostic biomarkers and therapies for children with brain tumors. CBTTC’s rapidly growing success and unprecedented molecular and genomic data generation efforts over the past year are achievements that meet objectives for our research community, years ahead of what was initially envisioned. These efforts demonstrate the success of our direct partnership with the community (parents, patients and clinicians alike) to constantly challenge and change the status quo.

This past year we launched CAVATICA (cavatica.org), initiated the genomic sequencing for the entire existing bank, and increased the CBTTC’s international collaborations to include Tiantan Hospital and the Chinese National Genebank. Such progress and expanded success was only possible through the unwavering partnership of families all over the world, and their willingness to participate and support specimen donation for children diagnosed with brain cancers. Additionally, it is only through the continuous financial support and advocacy of patients and their families that has enabled the expansion of our existing infrastructure to house, process, and share specimens and molecular data across the globe. A final and equally important contributing factor has been the strong and growing support from the research and clinical communities. This partnership and support of our initiatives continues to foster collaborations, even beyond the consortium’s current membership. We are excited to welcome Amanda Haddock of Dragon Master Foundation in her role as Liaison to the Scientific Committee to improve communication among foundation partners and provide updates on CBTTC scientific projects and discoveries.

In the coming year, we intend to build upon our shared success and achieve the following: 1) expand the existing membership nationally and internationally, 2) scale our generation of genomic data across all pediatric brain cancer types to increase the molecular data-types being generated, 3) partner across member institutions to test and validate preclinical models including patient-derived xenografts and cell lines, and 4) work closely with our partnered clinical trial network of PNOC and other clinical networks to translate validated molecular pathways to the clinical setting.

We are excited for the 2017-2018 and expect it to be a transformational tipping point for the CBTTC’s vision. We very much look forward to working with our colleagues, patient families, and foundations in our relentless journey to accomplish our vision of curing childhood brain cancers through new and less toxic treatments. We excitedly look forward to our shared progress over the coming year.


Adam Resnick, PhD & Javad Nazarian, PhD


Biospecimens received


Clinical & Specimen Data

The CBTTC has enrolled 2,170 patient subjects and contains 21,873 specimens, all highly annotated with clinical data and available for request by researchers across the world.

Specimen Collection

All specimens collected by the CBTTC are considered a gift from our donors and their families. The specimen and accessioning process follows a detailed workflow to ensure that donated biospecimens are preserved for later use by researchers. Each specimen is collected and stored with the utmost care and respect.

Data Access

The CBTTC supports data sharing and collaborative discovery through CBTTC-supported portals/platforms, NIH-supported portals/platforms, or other public platforms with approved security and patient privacy protection. The CBTTC adheres to NIH guidelines for genomic data sharing.

CBTTC Biorepository

The CBTTC biorepository boasts a state of-the-art automated sample storage system within a carefully monitored -20°C temperature and humidity-controlled environment. The REMP sample management system has a storage capacity of more than 2 million samples. Liquid nitrogen storage tanks provide space for an additional 1.6 million samples at -80°C.


Year in Review

The 2016-2017 fiscal year has been marked by a number of notable accomplishments by members of the Children’s Brain Tumor Tissue Consortium. The growth of the CBTTC’s leadership team expanded the reach of the consortium to include experts in pediatric brain tumor research in Europe, Asia and throughout the United States. Dr. Rishi Lulla of Ann and Robert H. Lurie Children’s Hospital in Chicago was named as the Chair of the Executive Board and Dr. Javad Nazarian of Children’s National Health System in Washington, D.C. joined Dr. Adam Resnick as the Co-Chair of the Scientific Committee. Additionally, Dr. Angela Waanders of Children’s Hospital of Philadelphia was named as the Director of Operations.

Under this strong leadership, the CBTTC has achieved steady and fiscally responsible growth. The CBTTC enrolled its 2,000th subject in 2016 and received more than 20,000 aliquots, or samples of specimens. These samples were almost immediately made available for research discovery. The CBTTC has grown to include 15 member institutions and support the vision and mission of the consortium. Joining the CBTTC as core members were Children’s National Health System in Washington D.C., Weill Cornell Medicine Pediatric Brain and Spine Center in New York, and Lucile Packard Children’s Hospital (Stanford University) in California. Joseph M. Sanzari Children’s Hospital at Hackensack University Medical Center in New Jersey joined as a satellite member. Additionally, the consortium expanded satellite membership to include institutions which contribute only genomic data. These institutions include Children’s Hospital of Orange County in California, University of California at Santa Cruz (Treehouse Childhood Cancer Initiative) in California, Beijing Tiantan Hospital Neurosurgery Center in China, and Genebank of Beijing Genomics Institute (BGI) in China.


saliva samplesThe past year marked a significant increase of the total number of biospecimens collected throughout the CBTTC, including the start of the saliva collection program from both par- ents and subjects. Saliva collection provides the CBTTC with a valuable resource — the ability to evaluate a subject’s DNA in the “germ- line” using saliva from both patients and their parents. In the past, germ-line analysis was performed using blood collections, which require both patients and family members to have blood drawn. Since the launch of the CBTTC in 2011, and as of the end of the last fiscal year, the total number of blood samples collected from patients and parents were few in number. In an effort to improve collection totals, saliva collection was introduced as a solution to provide a non-invasive method and logistically more-convenient alternative for germ-line testing. The CBTTC now has over 110 saliva samples collected from maternal and paternal donors, as well as subjects, with many more on the way.

Platform Development

To support scientific discovery, the CBTTC is collaborating with the Pacific Pediatric Neuro-Oncology Consortium (PNOC), a network of 15 member institutions that conduct clinical trials on children with brain tumors using a precision medicine approach. The results of this research and correlative biological data, which includes whole genome sequencing, are continually shared between the CBTTC and PNOC to support the identification of targeted therapies.

CAVATICAOne of the landmark achievements of this past year was the launch of CAVATICA, the first ever pediatric genomic cloud, in sup- port of the mission of the CBTTC. Named for the spider from the popular children’s story, Charlotte’s Web, CAVATICA was officially launched in October 2016 in conjunction with PNOC and Seven Bridges. The CAVATI- CA platform houses genomic datasets across different disease types, allowing analysis of genomic data to be performed in real-time. This online platform eliminates the need to ship external hard drives and data between institutions. The data within CAVATICA can be accessed much like Netflix, allowing re- searchers to connect to a cloud environment and to manipulate the data to build analysis pipelines within the platform. Not only does CAVATICA support accessibility, it further supports the vision of the CBTTC by granting open access to data for research efforts all over the world. Additionally, CAVATICA allows researchers to learn how the data was analyzed, increasing the reproducibility of results.

data dashboard

Among the many datasets already in CAVATICA, the biospecimens from within the CBTTC are currently undergoing whole genome sequencing and/or RNA sequencing for over 1,700 subjects. This data will be compiled to form the first-ever Pediatric Brain Tumor Atlas, and will be accessible to researchers across the globe. Along with the launch of CAVATICA, former Vice President Joe Biden delivered his Can- cer Moonshot report in October. During the report, the launch of CAVATICA was men- tioned as part of private sector commitments in his call to action to advance the goals of the Cancer Moonshot initiative. The an- nouncement can be found here.

Scientific Project Updates

The CBTTC continued to support researchers with eight additional approved projects, with any data generated being deposited into CAVATICA. The following projects were approved, bringing the total to 19.

Project 0012 – CBTTC Members: Whole Genome and RNA Sequencing of biospecimens within the biorepository, totaling more than 1,700 subjects.

Project 0013 – Dr. Mateusz Koptyra: Gene expression analysis platform evaluation for FFPE specimen material based studies

Project 0014 – Dr. Mateusz Koptyra: Evaluation of immunosignature profile in medulloblastoma

Project 0015 – Dr. Brian Rood: Proteogenomic Identification of Structural Variations

Project 0016 – Dr. Javad Nazarian and Dr. Heloisa Moser: Comprehensive Molecular Analysis of Pediatric Thalamic tumors

Project 0017 – Dr. Ian Pollack and Dr. Sameer Agnihotri: Integrated Genomic Analysis to elucidate the role of PIKC3A and 10q LOH as Unique drivers and cooperating events in pediatric high grade gliomas

Project 0018 – Dr. Frank Balis: Development of the ganglioside GD2 as a biomarker and clinical trial endpoint for childhood cancers

Project 0019 – Dr. Javad Nazarian, Dr. Brian Rood, and Dr. Paul Northcott: Integrative functional genomics of recurrent childhood medulloblastoma.

CBTTC Advisory Council

The CBTTC Advisory Council was created in 2016-2017 to help support the increasing needs of the CBTTC’s mission to discover better treatments and cures for children diagnosed with brain tumors. The council is currently comprised of 15 partner foundations located throughout the United States and represents a diversity of expertise and resources in support of the CBTTC’s research efforts. The council is a unique coalition of funders who have agreed to collaborate to maximize the impact of their support to the CBTTC. Advisory Council member foundations advise the CBTTC in several areas and provide direction to improve messaging and communication for various audiences to determine how the CBTTC can best meet the needs of the funding community.

A liaison to the executive committee is appointed for a two-year term and is responsible for representing the Advisory Council to the CBTTC leadership team. Additionally, a member of the Advisory Council is appointed as a liaison to the CBTTC Scientific Committee. The CBTTC leadership team is excited to welcome Allen Gustafson of the Swifty Foundation as the Advisory Council’s Liaison to the Executive Committee and Amanda Haddock of the Dragon Master Foundation as Liaison to the Scientific Committee.

Advisory Council membership is open to any foundation or individual who is interested in supporting the CBTTC. To apply for membership, email cbttcadmin@email.chop.edu.

The Advisory Council emphasizes the following areas of support:

1) Provide financial support of CBTTC operations at each of the participating member institutions. This includes funding the development of new therapies, research methods and technology to allow for improved patient care.

2) Promote and share the mission of the CBTTC throughout the scientific, biomedical and technology communities, including outreach to partner institutions and organizations.

3) Create educational and training opportunities for clinical and scientific members for CBTTC member institutions.

Members of the CBTTC Advisory Council include:

  • Alexander Munoz Memorial Fund
  • At Least Kids Foundation
  • Christopher Brandle Joy of Life Foundation
  • Children’s Brain Tumor Foundation
  • Christopher Court Foundation
  • Cure DIPG 4 Hope Foundation
  • Kyle Daniel Kerpan Foundation
  • Dragon Master Foundation
  • Grayson Saves Foundation
  • Kortney Rose Foundation
  • Lilabean Foundation for Pediatric Brain Tumor Research
  • Ross K. MacNeil Foundation
  • Swifty Foundation
  • Thea’s Star of Hope
  • Wylie’s Day Foundation

3rd Annual CBTTC Investigator Meeting

Over 100 investigators, data scientists and foundation partners attended the 3rd Annual CBTTC Investigator Meeting, which was held on the campus of The George Washington University in Washington, D.C. on May 7-8, 2017. The Investigator Meeting brought together researchers from each of the CBTTC’s 15 member institutions located across the United States and around the globe. Investigators presented updates about the CBTTC’s scientific projects and the current landscape of pediatric brain tumor research.

Sunday evening, of May 7th, principal investigators and foundation partners joined together to learn more about the improvements that the research of the CBTTC is making for children diagnosed with a brain tumor. Keynote speaker Mark Miller of the Smashing Walnuts foundation spoke of his daughter Gabriella’s efforts to bring together supporters from around the country to raise awareness for pediatric cancer research. Additionally, he addressed the need for advocacy and increased research funding on behalf of children.

During Monday’s scientific presentations, Dr. Roger Packer and Dr. Brian Rood, of Children’s National Health System in Washington D.C. delivered the keynote address before Monday’s scientific presentations, with Dr. Annie Huang of The Hospital for Sick Children in Toronto, Canada delivering the scientific keynote. Many investigators and foundation supporters participated in video interviews to highlight their organization’s role in the CBTTC’s research. Presentations from the Investigator Meeting are available on the CBTTC website.

Financial Reporting: 2016-17

The CBTTC leadership and members prioritized sound fiscal responsibility in order to support the vision and objectives of the consortium. The CBTTC is primarily supported through the philanthrophic efforts of all of its dedicated donors (70% of budget). Additional infrastructure funding resources are provided by the Children’s Hospital of Philadelphia (30% of budget), including the Division of Neurosurgery and the Center for Data-Driven Discovery in Biomedicine. The FY17 budget totalling $1,112,442.00 was broken down into the following core areas:

  • Personnel
  • Supplies
  • Travel
  • Subcontracts (Site Support)
  • Cores (Biorepository Core)
  • Equipment
  • Other (Includes annual Investigator Meeting)

A majority of donor funds, approximately $500,000, have been directed toward site support, with remaining donations providing support in the other core areas*. To ensure continued fiscal responsibility and as part of the CBTTC FY18 objectives, the Executive Board will continue to evaluate site participation through metric reporting to ensure full participation in the consortium.

*Note: Other resources provided by Children’s Hospital of Philadelphia, not reflected in these numbers, include use of the Hospital’s state-of-the-art biorepository, bioinformatics platforms, additional staff support from the more than 50 members of the Center for Data Driven Discovery, and gift processing and donor relations support from the CHOP Foundation.

Financial reporting

A Look Ahead: 2017-18

Looking forward to another year of growth and success, the CBTTC Executive Board identified multiple objectives for this coming fiscal year. The objectives include a focus on process improvements at the Operations Center, continued support of scientific discovery, and the sustainability and growth of the consortium.

1. To Improve Operations Center Processes

  •  Develop new tools to optimize operations
    • Design Operations Center Dashboard
    • Implement a Quality Control Tool for Clinical Data
  • Continue to improve practices to facilitate scientific project requests and biospecimen/data distribution
  • Facilitate regularly scheduled Clinical Working Group meetings to improve existing data and consider additional data elements
  • Development of Clinical Genomic Diagnostic Working Group

2. To Increase CBTTC Scientific Productivity

  • Completion of the Pediatric Brain Tumor Atlas sequencing project
  • Increase the CBTTC’s visibility at scientific meetings
  • Submit 3-4 peer-reviewed original scientific publications
  • Increase our capacity to generate patient derived cell lines and pre-clinical models
  • Intersect pediatric central nervous system tumor data with other diseases to enhance developmental biology discovery

3. To Develop a Sustainable Consortium and Support Growth

  • Apply for 1-2 major infrastructure grants
  • Offer a “Request for Proposal” and on-board an additional full member site
  • Define clear metrics for site participation in the CBTTC
  • Engage with the Advisory Council to explore novel funding strategies

Post-Mortem Tissue Donation Program

When parents lose a child to a brain tumor, there is often a drive to find meaning in their loss. Tissue donation for future research can provide a degree of comfort for those parents. The Post Mortem Tissue Program will be officially launched throughout the United States in May 2017. This program will provide parents the opportunity to donate tissue at no cost to them, even if a child passes at home. Aside from managing the logistical issues prior to and following death, each person involved, including clinical staff, will be provided with educational materials and resources about the Post Mortem Tissue Donation Program. The tissue donations will either be deposited into the CBTTC biorepository and/or sent to a local lab for immediate cell line generation and patient-derived xenografts (PDX) models.

The generation of these samples will support scientific discovery and ultimately advance the vision of the CBTTC to discover better therapies and cures. The project was inspired and is being funded by the Swifty Foundation. Brain tumor patients who elect to donate their tissue to the CBTTC’s Post-mortem Tissue Donation Program are providing researchers with the tumor tissue specimens they need to understand how brain tumors form on a bio- logical level. Without a critical mass of brain tumor tissue samples, scientists cannot fully understand how tumors behave or how to prevent them. Understanding more about each unique tumor type allows doctors to pre- scribe specific treatments for each individual child based on their specific needs. This helps to minimize the harmful side-effects of many currently-available treatments and increases the quality of life for children diagnosed with these diseases.

The CBTTC Post-mortem Tissue Program allows patients and family to empower pediatric brain tumor research. The following process makes tissue donation possible at locations throughout the United States:

1) Families must provide written consent to donate tumor tissue before the time of death and will receive one phone call at the time of death to confirm donation.

2) Within 24 hours, three different experts – an autopsy technician, a pathologist, and a research technician – must retrieve and process tissue for a successful donation. Patient families will never be charged for this service directly or through their insurance providers.

3) The tissue is processed and anonymous genomic (gene) and proteonomic (protein) data is cross-indexed and shared with other scientists throughout the consortium. This data is accessible to researchers all over the world for use in discovery efforts.

Download the 2016-17 CBTTC Annual Report (PDF)