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Scientific Background of the Children's Brain Tumor Tissue Consortium

November 30, 2009

Background

Recent advances in breast cancer, colon cancer, and melanoma treatment show the importance of detailed molecular analysis of tumor samples to find new therapeutic targets. By comparison, progress in the molecular characterizations of childhood brain tumors is much slower. The majority of these studies focus on medulloblastoma and high-grade gliomas but neglect other important childhood tumor histologies. In past years, we expected that cooperative “tissue banks” would meet childhood brain tumor research needs for large numbers of tissue samples. Unfortunately, this has not occurred due to poor accrual, lack of institutional incentive, institutional research competition, inefficient tissue use, and the absence of clinical data associated with the tumor specimens. In addition, none of the existing “tissue banks” collect matched viable tumor samples in order to develop tumor models in tissue culture or in mice. To address this problem, we will develop a new multi-institutional collaborative childhood brain tumor tissue research platform that will meet current needs for high-quality brain tumor biopsy samples, comprehensive clinical data, and new tumor model development.
 

Plans

Five institutions selected based on a high volume of childhood brain tumor surgical specimens and strong laboratory research programs utilizing genomic analysis will initiate the Children’s Brain Tumor Tissue Consortium: Children’s Hospital of Philadelphia (Tom Curran, P.I.), Children’s Hospital of Pittsburgh (Ian Pollack, P.I.), and Children’s Memorial Hospital Chicago (Stewart Goldman, P.I.), University of Washington (Seattle; Russell Geyer, PI) and New York University School of Medicine (David Zagzag, P.I.). In years 2-5, membership will be expanded to include three additional institutions. This consortium will be successful only with strong extrinsic incentives (including financial support for the surgical effort required to obtain sufficient high-quality tissue, tissue handling, pathology efforts, tissue processing, tissue shipping, data management) together with strong intrinsic incentives (including early access to high-quality, high sample size brain tumor material, new brain tumor models, and relevant clinical data.
 
We will collect and analyze all types of childhood brain tumors. Based on current patient numbers at the five institutions, we project that approximately 200 tumor specimens will be submitted for analysis during the first year and, with three additional members that approximately 2,000 brain tumor specimens of all histologies will be submitted within the first five years.
 
All tumor tissue genetic and protein will be performed at CHOP using the facilities of the Center for Genomic Analysis. We will also profile constitutional DNA from parental samples for future genetic studies as some pediatric tumors arise in syndromic patients and there is interest in determining factors that predispose children to brain tumors. Tissue Micro Arrays will be generated from as many samples as possible for use in biomarker follow-up and validation studies. Protein extracts will be prepared from blood, CSF and tumor samples for proteomic studies. All data, genomic, pathology and clinical, will be encoded using a common de-identification system to allow cross-platform comparisons. In addition, fully developed and characterized tumor models will be made available to all CBTTC members. We expect that a subset of the biopsy specimens will be available and suitable for this approach. Our initial goal is to obtain 3 or more models for each molecular subtype of tumor. 
 
After the non-clinical data is sent to participating institutions, it will be posted on a separate web site for universal access. We will also collaborate with caBIG and other data sharing organizations to ensure the robustness of shared data.
 

Summary

The Children’s Brain Tumor Tissue Consortium is a new research platform which actively stimulates tissue-based research, increases worldwide access to the molecular analysis of large numbers of brain tumor specimens, provides relevant, clinical data linked to those specimens, and facilitates the development of new experimental tumor models for use in pre-clinical therapy assessments.

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