Personal Statement for PCF Progress Report

Medulloblastoma is the most common malignant childhood brain tumor and yet very little is known about why it occurs in specific individuals. PCF funding of our proposal entitled “Medulloblastoma Risk and the Germline Foundation of Predisposition” has allowed us to leverage a wealth of Next Generation Sequencing data that has recently become accessible to the research community. Importantly, this sequencing data includes germline DNA sequencing which is the normal DNA in the body. With this resource, we can ask questions about who is at risk for the development of various cancers, questions that have been very difficult to answer in the past. PCF funding has made it possible for my lab to form a very important collaboration with a computer science and bioinformatics group at Virginia College of Osteopathic Medicine (VCOM) in order to bring to bear advanced programming to analyze this massive cache of data in an exhaustive and rigorous way. Our groups work very well together as they bring the programming skills and we provide the biological understanding and knowledge of translational utility to the project. This partnership has allowed my lab to expand in this new direction with very significant results. In addition, we have learned a lot from each other and my lab has expanded its genomics capabilities as a result. Beyond traditional germline mutations, our findings represent the first meaningful attempt to explain that the risk for medulloblastoma is linked to the normal healthy germline DNA of an individual person. We have recently published a manuscript from these efforts in a highly impactful journal – Neuro-Oncology. This publication will help to establish our expertise in this area in the context of achieving further grant funding. It will also highlight for the scientific community the contribution of non-coding DNA toward the formation of cancer. We are planning to jointly write an NIH funding proposal based upon these findings with the Garner lab at VCOM. This would not have been possible without the support of PCF.

Lay Statement of Impact

Cancer prevention is critically dependent upon identifying a population at risk for the cancer to be prevented. This applies to efforts to limit exposure to environmental carcinogens but also to screening and early detection programs. With high incidence cancers like colon, breast and prostate cancer, screening efforts are most commonly targeted to individuals based upon age and family history. However, this is much more difficult to do with more rare cancers like childhood cancers. Our identification of a group of DNA markers capable of distinguishing individuals with medulloblastoma from healthy subjects based only upon the DNA found in a blood sample is a significant first step in achieving this aim. While our findings are not yet sensitive and specific enough to be deployed in a large scale screening program, our initial work brings us closer to being able to identify individuals at risk for rare but no less devastating cancers. In addition to this potential, the establishment of the biological influence of specific microsatellites upon their companion genes could delineate avenues for preventative intervention.

Sarah Howard Childhood Cancer Fund

Prevent Cancer Foundation, 1600 Duke Street, Suite 500