PROJECT SUMMARY

• Determine the clinical impact of somatic genetic abnormalities in a cohort of 1393 adult and pediatric MOS patients who have undergone allogeneic stem cell transplantation.
• Identify mutations in a panel of 120 genes, including 70 genes that are recurrently mutated in myeloid malignancies and 50 genes that are mutated in inherited and acquired bone marrow failure syndromes.
• Identify associations between point mutations and post-transplant clinical outcomes, including disease progression or relapse, progression-free survival, non-relapse mortality, and overall survival, as well as other clinicopathologic features.
• Develop a comprehensive MOS genetic resource that is available to the Center for International Blood and Marrow Transplant Research (CIBMTR) community. The goal of this project is a definitive and potentially clinical practice-changing analysis of genetic predictors of outcome following allogeneic stem cell transplantation for MOS. Our previous work indicates that specific somatic mutations powerfully predict mortality following HSCT. The proposed study would validate these findings in a definitive cohort, the large repository of samples from the CIBMTR of MOS patients who underwent HSCT. In addition, MOS samples from the CIBMTR would be annotated with mutation status for the full spectrum of point mutations in MOS, enabling current and future investigators to explore the relationship between genetic lesions and clinical phenotype.