Mutational Signature in Cancers Following Solid Organ or Allogeneic Stem Cell Transplantation

Abstract

Transplant recipients are at a heightened risk of cancer, yet the full spectrum of etiologic factors is poorly understood. In this study, we analysed the mutational patterns in a clinically diverse cohort of 41,874 cancers and identified a mutational signature highly associated with a history of solid organ or allogeneic stem cell transplantation. This signature is characterized by a high tumor mutation burden and a striking predominance of C>A single base substitutions, particularly in the 5′-C[C>A]A-3′ trinucleotide context. We identified 13 transplant recipients whose tumors harbored this signature, which is distinct from previously described mutational processes, including those related to tobacco, defective DNA repair, or polymerase mutations. The discovery of this signature points to a mutagenic force in this vulnerable patient group and provides new insights into the pathogenesis of transplant-associated malignancies.