title: Genetic landscape of T- and NK-cell post-transplant lymphoproliferative disorders.
abstract: 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.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Margolskee
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Vaidehi
authors.initials: V
authors.lastname: Jobanputra
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Preti
authors.initials: P
authors.lastname: Jain
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Jinli
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Karthik
authors.initials: K
authors.lastname: Ganapathi
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Odelia
authors.initials: O
authors.lastname: Nahum
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Brynn
authors.initials: B
authors.lastname: Levy
authors.affiliation: Department of Pathology, Translational Cell and Tissue Research Laboratory, UZ Leuven/KU Leuven, Leuven, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Morscio
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Vundavalli
authors.initials: V
authors.lastname: Murty
authors.affiliation: Department of Pathology, Translational Cell and Tissue Research Laboratory, UZ Leuven/KU Leuven, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tousseyn
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Bachir
authors.initials: B
authors.lastname: Alobeid
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Mansukhani
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000502:physiology*
keywords: T-cell lymphoma; genetic; genomic; immunodeficiency; post-transplant lymphoproliferative disorders