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Pediatric High Grade Glioma Resources From the Children’s Brain Tumor Tissue Consortium (CBTTC) and Pediatric Brain Tumor Atlas (PBTA)

Heba Ijaz, Mateusz Koptyra, Krutika S. Gaonkar, Jo Lynne Rokita, Valerie P. Baubet, Lamiya Tauhid, Yankun Zhu, Miguel Brown, View ORCID ProfileGonzalo Lopez, Bo Zhang, View ORCID ProfileSharon J. Diskin, View ORCID ProfileZalman Vaksman, Children’s Brain Tumor Tissue Consortium, Jennifer L. Mason, Elizabeth Appert, Jena Lilly, Rishi Lulla, Thomas De Raedt, Allison P. Heath, Alex Felmeister, Pichai Raman, Javad Nazarian, Maria Rita Santi, Phillip B. Storm, Adam Resnick, Angela J. Waanders, Kristina A. Cole
doi: https://doi.org/10.1101/656587
Heba Ijaz
1Division of Oncology, Department of Pediatrics, Children’s Hospital of Philadelphia
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Mateusz Koptyra
23
3The Children’s Brain Tumor Tissue Consortium (CBTTC), Operations Center at the Children’s Hospital of Philadelphia
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Krutika S. Gaonkar
4Department of Biomedical and Health Informatics (DBHi), Children’s Hospital of Philadelphia
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Jo Lynne Rokita
23
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Valerie P. Baubet
23
3The Children’s Brain Tumor Tissue Consortium (CBTTC), Operations Center at the Children’s Hospital of Philadelphia
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Lamiya Tauhid
23
3The Children’s Brain Tumor Tissue Consortium (CBTTC), Operations Center at the Children’s Hospital of Philadelphia
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Yankun Zhu
23
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Miguel Brown
23
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Gonzalo Lopez
1Division of Oncology, Department of Pediatrics, Children’s Hospital of Philadelphia
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Bo Zhang
23
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Sharon J. Diskin
1Division of Oncology, Department of Pediatrics, Children’s Hospital of Philadelphia
4Department of Biomedical and Health Informatics (DBHi), Children’s Hospital of Philadelphia
7The Perelman School of Medicine, University of Pennsylvania
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  • ORCID record for Sharon J. Diskin
Zalman Vaksman
1Division of Oncology, Department of Pediatrics, Children’s Hospital of Philadelphia
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  • ORCID record for Zalman Vaksman
Jennifer L. Mason
23
3The Children’s Brain Tumor Tissue Consortium (CBTTC), Operations Center at the Children’s Hospital of Philadelphia
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Elizabeth Appert
23
3The Children’s Brain Tumor Tissue Consortium (CBTTC), Operations Center at the Children’s Hospital of Philadelphia
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Jena Lilly
23
3The Children’s Brain Tumor Tissue Consortium (CBTTC), Operations Center at the Children’s Hospital of Philadelphia
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Rishi Lulla
8Division of Hematology/Oncology, Hasbro Children’s Hospital, Department of Pediatrics, The Warren Alpert School of Brown University
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Thomas De Raedt
6Department of Pathology, Children’s Hospital of Philadelphia
7The Perelman School of Medicine, University of Pennsylvania
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Allison P. Heath
23
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Alex Felmeister
4Department of Biomedical and Health Informatics (DBHi), Children’s Hospital of Philadelphia
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Pichai Raman
4Department of Biomedical and Health Informatics (DBHi), Children’s Hospital of Philadelphia
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Javad Nazarian
3The Children’s Brain Tumor Tissue Consortium (CBTTC), Operations Center at the Children’s Hospital of Philadelphia
10Division of Hematology, Oncology, and Stem Cell Transplant, Ann & Robert H Lurie Children’s Hospital of Chicago, Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chicago, IL
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Maria Rita Santi
6Department of Pathology, Children’s Hospital of Philadelphia
7The Perelman School of Medicine, University of Pennsylvania
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Phillip B. Storm
23
3The Children’s Brain Tumor Tissue Consortium (CBTTC), Operations Center at the Children’s Hospital of Philadelphia
5Department of Neurosurgery, Children’s Hospital of Philadelphia
7The Perelman School of Medicine, University of Pennsylvania
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Adam Resnick
23
3The Children’s Brain Tumor Tissue Consortium (CBTTC), Operations Center at the Children’s Hospital of Philadelphia
5Department of Neurosurgery, Children’s Hospital of Philadelphia
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Angela J. Waanders
23
3The Children’s Brain Tumor Tissue Consortium (CBTTC), Operations Center at the Children’s Hospital of Philadelphia
10Division of Hematology, Oncology, and Stem Cell Transplant, Ann & Robert H Lurie Children’s Hospital of Chicago, Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chicago, IL
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Kristina A. Cole
1Division of Oncology, Department of Pediatrics, Children’s Hospital of Philadelphia
7The Perelman School of Medicine, University of Pennsylvania
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  • For correspondence: colek@email.chop.edu
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ABSTRACT

Background Pediatric high grade glioma (pHGG) remains a fatal disease. Increased access to richly annotated biospecimens and patient derived tumor models will accelerate pHGG research and support translation of research discoveries. This work describes the pediatric high grade glioma set of the Children’s Brain Tumor Tissue Consortium (CBTTC) from the first release (October 2018) of the Pediatric Brain Tumor Atlas (PBTA).

Methods pHGG tumors with associated clinical data and imaging were prospectively collected through the CBTTC and analyzed as the Pediatric Brain Tumor Atlas (PBTA) with processed genomic data deposited into PedcBioPortal for broad access and visualization. Matched tumor was cultured to create high grade glioma cell lines analyzed by targeted and WGS and RNA-seq. A tissue microarray (TMA) of primary pHGG tumors was also created.

Results The pHGG set included 87 collection events (73 patients, 60% at diagnosis, median age of 9 yrs, 55% female, 46% hemispheric). Analysis of somatic mutations and copy number alterations of known glioma genes were of expected distribution (36% H3.3, 47% TP53, 24% ATRX and 7% BRAF V600E variants). A pHGG TMA (n=77), includes 36 (53%) patient tumors with matched sequencing. At least one established glioma cell line was generated from 23 patients (32%). Unique reagents include those derived from a H3.3 G34R glioma and from tumors with mismatch repair deficiency.

Conclusion The CBTTC and PBTA have created an openly available integrated resource of over 2,000 tumors, including a rich set of pHGG primary tumors, corresponding cell lines and archival fixed tissue to advance translational research for pHGG.

IMPORTANCE OF STUDY High-grade gliomas (HGG) remain the leading cause of cancer death in children. Since molecularly heterogeneous, preclinical studies of pediatric HGG will be most informative if able to compare across groups. Given their relatively rarity, there are few readily available biospecimens and cellular models to inform preclinical laboratory and genomic translational research. Therefore, the aim of this CBTTC study was to highlight the panel of pediatric HGG cases whose primary tumors have undergone extensive genomic analysis, have clinical data, available imaging and additional biospecimens, including tumor, nucleic acids, cell lines and FFPE tissue on a tissue microarray (TMA).

Footnotes

  • Conflict of Interest: none

  • Authorship: Conception or design of the work: HI, MK, PR, SD, AR, AW, KC Acquisition, analysis, or interpretation of data for the work: HI, MK, VB, LY, KG, JLR, GG, PR, YZ, MB, BZ, JM, JL, RL, AF, JN, MS, PS, AR, AW, KC Manuscript preparation and review: all authors

  • https://cbttc.org

  • https://eig.research.chop.edu/cbttc/

  • https://kidsfirstdrc.org

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 31, 2019.
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Pediatric High Grade Glioma Resources From the Children’s Brain Tumor Tissue Consortium (CBTTC) and Pediatric Brain Tumor Atlas (PBTA)
Heba Ijaz, Mateusz Koptyra, Krutika S. Gaonkar, Jo Lynne Rokita, Valerie P. Baubet, Lamiya Tauhid, Yankun Zhu, Miguel Brown, Gonzalo Lopez, Bo Zhang, Sharon J. Diskin, Zalman Vaksman, Children’s Brain Tumor Tissue Consortium, Jennifer L. Mason, Elizabeth Appert, Jena Lilly, Rishi Lulla, Thomas De Raedt, Allison P. Heath, Alex Felmeister, Pichai Raman, Javad Nazarian, Maria Rita Santi, Phillip B. Storm, Adam Resnick, Angela J. Waanders, Kristina A. Cole
bioRxiv 656587; doi: https://doi.org/10.1101/656587
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Pediatric High Grade Glioma Resources From the Children’s Brain Tumor Tissue Consortium (CBTTC) and Pediatric Brain Tumor Atlas (PBTA)
Heba Ijaz, Mateusz Koptyra, Krutika S. Gaonkar, Jo Lynne Rokita, Valerie P. Baubet, Lamiya Tauhid, Yankun Zhu, Miguel Brown, Gonzalo Lopez, Bo Zhang, Sharon J. Diskin, Zalman Vaksman, Children’s Brain Tumor Tissue Consortium, Jennifer L. Mason, Elizabeth Appert, Jena Lilly, Rishi Lulla, Thomas De Raedt, Allison P. Heath, Alex Felmeister, Pichai Raman, Javad Nazarian, Maria Rita Santi, Phillip B. Storm, Adam Resnick, Angela J. Waanders, Kristina A. Cole
bioRxiv 656587; doi: https://doi.org/10.1101/656587

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