Genetic landscape of T- and NK-cell post-transplant lymphoproliferative disorders
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Elizabeth Margolskee1, Vaidehi Jobanputra1, Preti Jain1, Jinli Chen1, Karthik Ganapathi1, Odelia Nahum1, Brynn Levy1, Julie Morscio2, Vundavalli Murty1, Thomas Tousseyn2, Bachir Alobeid1, Mahesh Mansukhani1,* and Govind Bhagat1,*
1 Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA
2 Department of Pathology, Translational Cell and Tissue Research Laboratory, UZ Leuven/KU Leuven, Leuven, Belgium
* These authors share senior co-authorship
Govind Bhagat, email:
Mahesh Mansukhani, email:
Keywords: post-transplant lymphoproliferative disorders, immunodeficiency, genetic, genomic, T-cell lymphoma
Received: April 27, 2016 Accepted: May 06, 2016 Published: May 27, 2016
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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