DEFINING GENETIC DRIVER MUTATIONS,CLINIC CHARACTERISTICS & OUTCOMES IN CHILDREN & YOUNG ADULTS WITH HISTIOCYTOSES
Mentor Name: Will Parsons
Histiocytic disorders are diverse hematologic and immunologic conditions that can affect multiple organs and lead to severe organ damage and death. Pediatric histiocytic disorders such as Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG), and Rosai-Dorfman Disease (RDD) combined are as common as pediatric Hodgkin lymphoma. Unfortunately, the mechanisms of pathogenesis remain largely undefined, and there are few insights to guide the development of optimal therapy. Conventional chemotherapy fails to cure over 50% of these patients and is associated with high toxicity rates. This research project aims to identify the genetic mutations that drive the formation of histiocytic lesions. Like LCH, we believe RDD and JXG are caused by mutations in MAPK pathway genes. We will perform genetic studies on RDD and JXG biopsy samples to identify the presence of any known or unknown mutations. Understanding the underlying cause of these disorders is necessary to properly treat patients and improve the outcomes in patients with the disease. In addition to the genetic information, we will provide detailed clinical information regarding patients’ disease presentation, disease sites, treatment attempts, and responses to treatment. We will ultimately use this information to design the best treatment strategies for these patients based on clinical presentation and mutation status.
