Kathy Warren, M.D., NCI
Special Project funded 2010-2011
Children with diffuse intrinsic pontine gliomas (DIPG) continue to have a poor outcome despite advances in radiation oncology, new chemotherapeutic agents and extensive research into overcoming drug resistance. One of the major obstacles is the lack of biological studies that may aid us in better understanding the disease. Surgical resection has no role for these tumors given the tenuous location, and biopsy is not routinely performed due to the perceived risk from the procedure, tumor heterogeneity, and the futility of obtaining tissue in a disease for which there is no adequate treatment.
However, tumor tissue from autopsies of these patients may be an alternate source. Although the tumor likely changed over time with treatment and further progression, autopsy tissue may be a starting point to learn about these tumors. We recently performed a study evaluating the feasibility of performing comparative genomic hybridization (CGH) on formalin-fixed paraffin-embedded (FFPE) samples of tumor tissue obtained from autopsy of DIPG children. CGH is a method that can identify changes in DNA and has been used as a tool to screen tumors for genetic changes.
Our results indicate that it is feasible to perform CGH on stored FFPE samples. All samples that underwent successful CGH demonstrated abnormal DNA. Most specimens showed more than one DNA abnormality related to a known cancer gene and these changes were often associated with a candidate drug target. However, there was considerable heterogeneity amongst patients with DIPG.
Because of these results, we are expanding this study to include high-grade gliomas, low-grade gliomas and additional DIPGs in an effort to better define the molecular and genetic abnormalities associated with each subtype, and potentially identify additional targets for therapy. Funding from the Childhood Brain Tumor Foundation will help defray the costs associated with transportation and performing the autopsy, so that inability to pay will not prevent a family from donating tumor tissue if they wish to do so. In addition, tumor tissue obtained from autopsies on these patients is shared with other researchers so that as much as possible is learned from each donation. CBTF will help defray the costs of shipping and handling these precious tissues.
We are grateful to the CBTF for helping to fund this project and assisting us in advancing our knowledge of this devastating disease.