title: Genomic profiling of Sézary syndrome identifies alterations of key T cell signaling and differentiation genes.
abstract: Sézary syndrome is a rare leukemic form of cutaneous T cell lymphoma characterized by generalized redness, scaling, itching and increased numbers of circulating atypical T lymphocytes. It is rarely curable, with poor prognosis. Here we present a multiplatform genomic analysis of 37 patients with Sézary syndrome that implicates dysregulation of cell cycle checkpoint and T cell signaling. Frequent somatic alterations were identified in TP53, CARD11, CCR4, PLCG1, CDKN2A, ARID1A, RPS6KA1 and ZEB1. Activating CCR4 and CARD11 mutations were detected in nearly one-third of patients. ZEB1, encoding a transcription repressor essential for T cell differentiation, was deleted in over one-half of patients. IL32 and IL2RG were overexpressed in nearly all cases. Our results demonstrate profound disruption of key signaling pathways in Sézary syndrome and suggest potential targets for new therapies.
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Linghua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ni
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Covington
authors.affiliation: Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Betty Y
authors.initials: BY
authors.lastname: Yang
authors.affiliation: Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Shiu
authors.affiliation: Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Liu
authors.initials: L
authors.lastname: Xi
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Qingchang
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Langridge
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jennifer
authors.identifier: http://orcid.org/0000-0002-2612-5958
authors.initials: J
authors.lastname: Drummond
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Donehower
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Harshavardhan
authors.initials: H
authors.lastname: Doddapaneni
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Wheeler
authors.affiliation: Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
mesh_terms: D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics*; D059472:Exome / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D040961:Genetic Drift; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008213:Lymphocyte Activation; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D012751:Sezary Syndrome / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*