"Using high-throughput genomic technologies and the principles of genetic epidemiology, our lab works to identify inherited causes of malignant brain tumors in children and adults. The Sontag Foundation's Distinguished Scientist Award will enable us to apply these techniques to uncovering the genes involved in medulloblastoma predisposition, potentially leading to improved risk stratification and a better understanding of the biologic pathways fundamental to tumor initiation."
- Dr. Kyle M. Walsh
- Assistant Professor, Department of Neurological Surgery, UCSF School of Medicine
About DSA-Funded Research
Medulloblastoma is the most common malignant brain tumor in children. Five year survival rates have climbed to 70%, but survivors still experience serious disabilities as a result of treatment. Although numerous studies have investigated the acquired mutations present in medulloblastoma tumors, little is known about inherited genetic factors underlying this deadly cancer. The identification of robust medulloblastoma risk factors can help reveal the biologic pathways involved in disease development. We will test the hypothesis that both rare and common genetic variants contribute to medulloblastoma risk, and to risk of specific medulloblastoma subgroups. To achieve this, we will conduct genome-wide analyses of rare and common inherited genetic variants using archived neonatal bloodspots from 850 Californian children diagnosed with medulloblastoma. To identify rare genetic risk factors, blood-derived DNA from 205 children with medulloblastoma will undergo targeted sequencing of 1,000 genes believed to be involved in medulloblastoma development. A significant enrichment of harmful variants in a single gene among affected children compared to cancer-free control children will indicate that the gene may be involved in medulloblastoma predisposition. To discover common genetic risk factors, DNA samples from all 850 children diagnosed with a medulloblastoma will be typed at one-million common genetic markers. A marker that is significantly more common in the affected children than in 5,000 cancer-free control children also undergoing genotyping is likely to tag genes involved in medulloblastoma susceptibility. This registry-based approach will obtain an unprecedentedly large sample size and can identify novel genes involved in medulloblastoma development.
"Kyle is one of the top young investigators I have mentored in my 30 year career and an ideal choice for a Sontag Foundation Distinguished Scientist Award. In addition to his excellent training in genetic epidemiology, he quickly absorbs and translates difficult concepts, easily forges new collaborations, and is exceptionally productive."
Margaret R. Wrensch, Ph.D., M.PH.
The University of California, San Francisco
"Kyle is a classically trained molecular epidemiologist with the requisite bioinformatics toolkit, and additionally has wet-lab experience in a clinical genetics lab. I believe that he is perhaps the field's best chance for sustained growth and success in pediatric brain tumor epidemiology."
Michael D. Taylor, M.D., Ph.D.
Sick Kids, The Hospital for Sick Children