NDLI: IDENTIFICATION AND PRELIMINARY TREATMENT DATA OF XENOGRAFTS REPRESENTING TCGA-DEFINED SUBTYPES

Content Provider	PubMed Central
Author	Keir, Stephen T. Roskoski, Martin A. Gasinski, Danuta Kwatra, Madan K. Friedman, Henry S. Bigner, Darell D.
Copyright Year	2014
Abstract	BACKGROUND: The Cancer Genome Atlas (TCGA) Network recently catalogued recurrent genomic abnormalities in glioblastoma (GBM). This genomic profiling lead to the molecular classification of GBMs into four subtypes: Proneural, Neural, Classical and Mesenchymal. The importance of identifying these subtypes stands to help researchers and clinicians to better understand GBMs with the potential to personalize treatment options and explore different therapeutic approaches that each subtype may require. As such, the development of preclinical xenograft models that represent each TCGA subtype serves to expedite the evaluation of targeted therapeutic strategies for the treatment of GBMs. METHODS: For this project, established xenografts from patient derived tissue were passaged until reliable growth characteristics were obtained. Established GBM xenografts were classified into TCGA-defined subtypes first by obtaining global gene expression data using Affymetrix. Microarray data was then normalized and probes were summarized as gene expression levels using RMA. Then data was log2 transformed and genes were median centered. Xenografts were subsequently classified into one of four previously defined subtypes as described using Classification to the Nearest Centroid (ClaNC) with the TCGA GBM training dataset. Using established xenografts from each subtype, a preliminary panel of treatment agents was assessed by delay in tumor growth and by tumor regression in athymic mice bearing subcutaneous tumors. Statistical analysis was performed using a personalized SAS statistical analysis program, the Wilcoxon rank order test for growth delay, and Fisher's exact test for tumor regression. RESULTS: To date, our lab has established and identified 2 patient derived xenografts for each TCGA-defined subtype. These xenografts lines have reliable growth patterns with a tumor take rate >80%. Phase I drug testing has been completed and includes tumor growth responses to the following single agents: temozolomide, bevacizumab, BCNU, cytoxan, and irinotecan. CONCLUSIONS: A panel of patient derived xenografts with reliable growth characteristics that represent the four TCGA-defined GBM subtypes has been established and utilized for drug evaluation. The identification of these valid xenograft models represents an important contribution for modeling and predicting therapeutic response. We have currently completed the first round of drug testing within each subtype and look to expand testing to include additional agents as well as select combinations. SECONDARY CATEGORY: n/a.
Related Links	http://dx.doi.org/10.1093/neuonc/nou208.45
Starting Page	35
File Format	PDF
ISSN	15228517
e-ISSN	15235866
Journal	Neuro-Oncology
Issue Number	Suppl 3
Volume Number	16
Language	English
Publisher	Oxford University Press
Publisher Date	2014-07-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Cancer Research Oncology Clinical Neurology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Neurology (clinical) Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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