Abstract
Four organ transplant recipients from an organ donor diagnosed with anaplastic pleomorphic xanthoastrocytoma developed fatal malignancies for which the origin could not be confirmed by standard methods. We identified the somatic mutational profiles of the neoplasms using next-generation sequencing technologies and tracked the relationship between the different samples. The data were consistent with the presence of an aggressive clonal entity in the donor and the subsequent proliferation of descendent tumors in each recipient. Deleterious mutations in BRAF, PIK3CA, SDHC, DDR2, and FANCD2, and a chromosomal deletion spanning the CDKN2A/B genes, were shared between the recipients' lesions. In addition to demonstrating that DNA sequencing tracked a donor/recipient cancer transmission, this study established that the genetic profile of a donor tumor and its potential aggressive phenotype could have been determined before transplantation was considered. As the genetic correlates of tumor invasion and metastases become better known, adding genetic profiling by DNA sequencing to the data considered for transplant safety should be considered.
Highlights
There has been a steady increase over the last decade in organ donation from deceased donors, there is still a significant discrepancy between organ availability and demand
We report a case of a young organ donor diagnosed with anaplastic pleiomorphic xanthoastrocytoma (PXA) and multiple organ recipients who developed aggressive neoplasms shortly after transplantation (Fig 1)
Based on targeted panel sequencing, the most frequent somatic mutations detected in PXA are BRAF, FANCA/D2/I/M, PRKDC, NF1, NOTCH2/3/4, and CDKN2A (Park et al, 2017; Zou et al, 2019)
Summary
There has been a steady increase over the last decade in organ donation from deceased donors, there is still a significant discrepancy between organ availability and demand. 32,321 recipients received organs from 11,870 donors in 2019, but 11,702 patients were removed from the transplant list because they died (5,604) or became too ill to qualify for a transplant (6,098). As of 11 October 2020, there were 119,465 patients remaining on the waiting list (https://optn.transplant.hrsa.gov/data/view-datareports/national-data/). For this reason, donors deceased after cancer of the central nervous system (CNS) are considered for donation, representing 0.3% of the donor pool. Transplantation of organs from a donor with a known malignancy carries potential risks of cancer transmission to immunosuppressed recipients. These risks vary depending on factors such as the type of tumor, the history of the malignancy and the treatment received. Guidelines on the safety of organs for transplantation have been issued, based on several published studies and reports from organ sharing registries of different countries (https://www.edqm.eu/en/guide-quality-and-safety-organstransplantation)
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