Kartik Singhal
Kartik is a graduate student in the Molecular Genetics and Genomics program at Washington University in St. Louis. He obtained his Bachelor of Science in Biotechnology at the University of California, Davis (2018). He is pursuing his thesis research in Malachi Griffith and Obi Griffith’s lab where he is interested in using multi-omic techniques to better understand the tumor microenvironment and cancer’s interaction with the immune system.
Abstract
Kartik Singhal, Marcus Watkins, Todd Fehniger, Malachi Griffith, Obi Griffith, Brad Kahl, David Russler-Germain
Washington University School of Medicine, St. Louis, MO, United States
Cancer incidence is increased in solid organ transplant recipients compared to the general population, including post-transplant lymphoproliferative disorders (PTLD). Here, we present an unusual case of a kidney transplant recipient who developed follicular lymphoma (FL) 12 years post-transplant at 39 years of age, shortly after the patient’s donor father also had developed FL at 60 years of age. These coincidental diagnoses motivated evaluation of the relatedness of these two cases of FL. Traditional FISH revealed the presence of a Y chromosome in the daughter’s tumor. Tumor-normal whole genome/exome sequencing for both FL cases confirmed the donor-origin of the daughter’s FL and revealed 31 shared mutations including identical variants in two key FL driver genes CREBBP and KMT2D. Furthermore, 76 and 133 unique mutations were identified in the recipient and donor tumors, respectively, indicating the divergence of the tumors that occurred after transfer of the pre-malignant cells at time of the kidney transplant. Interestingly, distinct variants in BTG1 and BTG2 were found in both FL tumors, suggesting possible shared mechanistic dependencies of the two lymphomas. While previous reports have documented donor-derived transmission of FL through lymphocyte infusion or allogeneic stem cell transplant, this is, to our knowledge, the first reported case of FL transmission via solid organ transplant. Further, the 12-year duration between the daughter’s kidney transplant and FL diagnosis highlights the prolonged period of serial mutation acquisition in this disease, as well as the discordance between the presence of driver gene mutations and the absence of clinically relevant disease.