In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 6144-6144
Abstract:
Pediatric brain tumors comprise a distinct spectrum of diseases compared to adult brain tumors and are distinguished by their unique clinical and histopathological features, developmental context, mutation burden, and genomic, epigenomic, and transcriptomic alterations. Access to in vivo models that recapitulate pediatric brain tumors has been limited and inadequate to represent these heterogeneous diseases. Here we introduce the Pediatric Brain Tumor Portal (PBTP, pbtp.stjude.cloud), an open resource to access molecular characterization, including whole-genome sequencing, whole-exome sequencing, RNA-seq, and DNA methylome profiling, of patient-derived orthotopic xenograft (PDOX) models of pediatric brain tumors. The portal will host more than 70 models, which currently include pediatric High-Grade Glioma (pHGG), Medulloblastoma, Atypical Teratoid/Rhabdoid Tumors (AT/RT), Ependymoma, and Embryonal Tumors with Multilayered Rosettes (ETMR), and reflects close to ten years of effort to generate and extensively characterize in vivo models that recapitulate primary pediatric brain tumors. PBTP is a database-driven and user-friendly platform that enables multi-omics views of PDOX and matched patient tumor and germline samples at multiple levels to help identify appropriate lines for studies of tumorigenesis or preclinical testing. To evaluate the representation of different molecular features within a disease subgroup, we implemented various visualization tools for searching and comparing somatic mutations, gene expression profiles, and methylation groups of our models and matched patient tumors. Details for each tumor including de-identified clinical data, histology, growth characteristics, DNA methylation classification, mutation status, and copy number variations are also readily available for side-by-side comparison. Furthermore, in vitro chemical sensitivity profiling is presented for selected models with matched cell lines. Users can investigate genes of interest for single nucleotide variants, small insertions and deletions, copy number variations, gene fusions, and mRNA expression in PDOX and matched patient tumors. This portal has been integrated into the St. Jude Cloud platform, through which users can explore patient and PDOX sequencing data in the context of larger cohort data sets and download raw genomics data files. PBTP provides a platform to share PDOX models with in-depth genome/epigenome-wide characterization to support advances in basic and translational research in pediatric brain tumors. *co-first, #co-corresponding Citation Format: Paige S. Dunphy, Ke Xu, Darrell T. Gentry, Chen He, Kimberly Mercer, Xiaoyan Zhu, Kyle Smith, Brian Gudenas, Sarah Robinson, Junyuan Zhang, Lawryn H. Kasper, Chang-Hyuk Kwon, Laura D. Hover, Jon D. Larson, Nathaniel Twarog, Aksana Vasilyeva, Nedra Robison, Daniel Alford, Cynthia Williams, Anthony Woodard, Xin Zhou, Edgar Sioson, J. Robert Michael, Austyn Trull, Irina McGuire, Brandon McMahan, Swapnali Mohite, Ashok Boddu, Kirby Birch, Clay McLeod, Michael A. Dyer, Paul Klimo, Frederick A. Boop, Amar Gajjar, Christopher L. Tinkle, Giles Robinson, Brent A. Orr, Jason Chiang, Paul A. Northcott, Jinghui Zhang, Keith Perry, Gang Wu, Anang A. Shelat, Ed Suh, Martine F. Roussel, Suzanne J. Baker. St. Jude Pediatric Brain Tumor Portal: Cloud-based resource for patient-derived orthotopic xenograft (PDOX) models of pediatric high-grade glioma, ependymoma, and CNS embryonal tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6144.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2020-6144
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2020
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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