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Genetic landscape of T- and NK-cell post-transplant lymphoproliferative disorders

Margolskee, Elizabeth; Jobanputra, Vaidehi; Jain, Preti; Chen, Jinli; Ganapathi, Karthik; Nahum, Odelia; Levy, Brynn; Morscio, Julie; Vundavalli, Murty V.; Tousseyn, Thomas; Alobeid, Bachir; Mansukhani, Mahesh M.; Bhagat, Govind

Post-transplant lymphoproliferative disorders of T- or NK-cell origin (T/NK-PTLD) are rare entities and their genetic basis is unclear. We performed targeted sequencing of 465 cancer-related genes and high-resolution copy number analysis in 17 T-PTLD and 2 NK-PTLD cases. Overall, 377 variants were detected, with an average of 20 variants per case. Mutations of epigenetic modifier genes (TET2, KMT2C, KMT2D, DNMT3A, ARID1B, ARID2, KDM6B, n=11). and inactivation of TP53 by mutation and/ or deletion (n=6) were the most frequent alterations, seen across disease subtypes, followed by mutations of JAK/STAT pathway genes (n=5). Novel variants, including mutations in TBX3 (n=3), MED12 (n=3) and MTOR (n=1), were observed as well. High-level microsatellite instability was seen in 1 of 14 (7%) cases, which had a heterozygous PMS2 mutation. Complex copy number changes were detected in 8 of 16 (50%) cases and disease subtype-specific aberrations were also identified. In contrast to B-cell PTLDs, the molecular and genomic alterations observed in T/ NK-PTLD appear similar to those reported for peripheral T-cell lymphomas occurring in immunocompetent hosts, which may suggest common genetic mechanisms of lymphoma development.

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Pathology and Cell Biology
Published Here
August 30, 2019