In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 6149-6149
Abstract:
Despite making significant advances over the past 25 years in our understanding of the most common adult solid tumors, much less is known about childhood solid tumors. We have previously described a protocol to produce orthotopic patient-derived xenografts (O-PDX) at diagnosis, recurrence and autopsy. These O-PDX models provide both in vivo and in vitro systems to study mechanisms of disease origin, tumor progression and preclinical testing. Here, we present an innovative cloud-based all-in-one data portal to explore various biological features of these pediatric O-PDX models. The vast diversity of the collected childhood solid tumors is represented in 166 O-PDX models, consisting of 21 diagnoses including Neuroblastoma, Osteosarcoma, Rhabdomyosarcoma, and a large number of rare solid tumors including Ewing Sarcoma, Desmoplastic Small Cell Round Tumor, Fibrosarcoma, High Grade Sarcoma, Liposarcoma, Retinoblastoma, Rhabdoid Tumor and Synovial Sarcoma. The O-PDX models have been characterized and compared to the original patient tumor using various methods and assays including histology, electron microscopy, short tandem repeat DNA profiling, chemical compound screening as well as genomic sequencing (whole genome sequencing, whole exome sequencing, and RNA Sequencing) and clonal analysis to determine the clonal population in the O-PDX. Somatic genetic mutations as well as clonal architecture is retained in the majority of O-PDX tumors. The data on O-PDX models can now be visualized and compared in our web-based CSTN data portal on St Jude Cloud (www.stjude.cloud). The user-friendly interface allows both gene and sample level search and visualization. For genomics variations, the presence or absence of a particular variant can be observed through interactive heatmaps. In addition to genomic and transcriptomic profiles, some of these models have extensive epigenomic and proteomic profiling which are integrated into the portal. We have also included chemical sensitivity heatmaps and dose response curves for common oncology drugs using primary cultures of the O-PDXs and cell lines. Importantly, the raw genomics sequencing data is also available from St Jude Cloud, following a straightforward application and approval process for access. In summary, the integration of data from multi-omics and beyond at the CSTN data portal provides a rich resource for both academic and industrial research community to find the appropriate models to advance the knowledge and therapeutic solutions to the catastrophic childhood solid tumors. *co-first #co-corresponding Citation Format: Asa Karlstrom, Ti-Cheng Chang, Darrell Gentry, Xin Zhou, Elizabeth Stewart, Brittney Gordon, Sara M. Federico, Rachel Brennan, Michael R. Clay, Sharon Frase, Armita Bahrami, Xiang Chen, Anang A. Shelat, Nathaniel R. Twarog, Daniel Alford, Anthony Woodard, Edgar Sioson, Irina McGuire, Cynthia Williams, Nedra Robison, Brandon McMahan, Ashok K. Boddu, Swapnali Mohite, Kirby Birch, Clay McLeod, Michael Rusch, Alberto Pappo, Keith Perry, Gang Wu, Ed Suh, Michael A. Dyer. An innovative integrated cloud-based data portal for orthotopic patient-derived xenografts (O-PDX) available through the Childhood Solid Tumor Network (CSTN) [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 6149.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2020-6149
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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