학술논문

Solid Organ Transplantation Is Associated with an Increased Rate of Mismatch Repair Deficiency and PIK3CA Mutations in Colorectal Cancer
Document Type
article
Source
Current Oncology, Vol 30, Iss 1, Pp 75-84 (2022)
Subject
mismatch repair deficient colon cancer
PIK3CA mutations
calcineurin Inhibitors
post-transplant malignancies
high tumor mutation burden tumors
immune surveillance
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Language
English
ISSN
1718-7729
1198-0052
Abstract
Solid organ transplants are associated with a modestly increased risk of colorectal cancers (CRC). However, the molecular profile of these cancers has not been described. We hypothesized that transplant-related immunosuppression may promote development of more immunogenic tumors as suggested by a high tumor mutation burden or mismatch repair deficiency. We performed an electronic medical record search for patients seen in the Johns Hopkins University Health System (JHHS) between 2017 and 2022 who developed CRC following solid organ transplantation. A comparator cohort of patients treated for CRC at JHHS with molecular profiling data was also identified. In this case, 29 patients were identified that developed post-transplant CRC (renal transplant, n = 18; liver transplant, n = 8; kidney-liver transplantation, n = 3). Compared to the JHHS general population CRC cohort, patients who developed post-transplant CRC had a higher rate of mismatch repair deficiency (41% versus 12%, p-value = 0.0038), and elevated tumor mutation burden (median of 22 mut/Mb versus 3.5 mut/Mb, p-value = 0.033) (range 3.52–53.65). Post-transplant tumors were enriched for PIK3CA mutations (43% versus 24%, p-value = 0.042). Post-Transplant CRCs are associated with clinical and molecular features of immune sensitivity, supporting a potential role for impaired immune surveillance in shaping the landscape of CRCs. These results may help inform the management of patients with post-transplant CRC.