Microsatellite analysis of posttransplant lymphoproliferative disorders: determination of donor/recipient origin and identification of putative lymphomagenic mechanism.

Abstract

The genetic mechanisms that give rise to posttransplant lymphoproliferative disorders (PTLDs) are not well established, yet previous studies have focused or) the role of immunosuppression and EBV infection. We investigated whether microsatellite analysis could: (a) determine the recipient/donor origin of the tumor; and (b) document novel genetic alterations in PTLDs, i.e., microsatellite instability. We characterized seven cases of PTLD (five B-cell and two T-cell non-Hodgkin's lymphomas) in which donor allograft tissue, normal recipient tissue, and tissue from the PTLDs were available. In each case, six microsatellite loci were analyzed. Five cases were of host origin (three B-cell and two T-cell lymphomas). The two cases of donor origin were B-cell lymphomas. Multiple loci showed microsatellite instability in two cases of host-derived T-cell non-Hodgkin's lymphomas (28% of PTLDs). These findings show that microsatellite analysis may be used to determine the host or donor origin of PTLDs and suggest for the first time that defective DNA mismatch repair may be an underlying genetic mechanism of lymphomagenesis in some cases of PTLD.