Post-transplant lymphoproliferative disorder (PTLD) is a malignant transformation of white blood cells called lymphocytes that occurs in solid-organ or tissue-transplant recipients, resulting in significant morbidity and mortality. Many PTLD cases are caused by the Epstein-Barr virus (EBV), but the remaining cases have no known cause. The goal is to study the underlying causes and predictors of clinical outcomes in EBV-positive and EBV-negative PTLD cases. Newly available next-generation deep shotgun sequencing technologies through the Washington University Genome Institute will be used to simultaneously detect many different known viral sequences from extracted stored PTLD tissue paraffin blocks. After also analyzing the associated clinical data, the following will be determined:
• In EBV-positive PTLD, the hypothesis that certain EBV genome sequence variants are associated with a more severe presentation or worse outcomes will be tested.
• In EBV-negative PTLD, whether genomic nucleic acid sequences of other known viruses are present in the tissue will be determined.
Potential impact: This high-risk multidisciplinary project could have a major impact in the field, potentially revealing not only the causes of EBV-negative PTLD cases, but also genomic variants that could be studied for future therapeutic targets.