Genomic profiling of Sézary syndrome identifies alterations of key T cell signaling and differentiation genes.

TitleGenomic profiling of Sézary syndrome identifies alterations of key T cell signaling and differentiation genes.
Publication TypeJournal Article
Year of Publication2015
AuthorsWang, L, Ni, X, Covington, KR, Yang, BY, Shiu, J, Zhang, X, Xi, L, Meng, Q, Langridge, T, Drummond, J, Donehower, LA, Doddapaneni, HV, Muzny, DM, Gibbs, RA, Wheeler, DA, Duvic, M
JournalNat Genet
Volume47
Issue12
Pagination1426-34
Date Published2015 Dec
ISSN1546-1718
KeywordsCase-Control Studies, Cell Differentiation, Exome, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Genetic Drift, Genomics, High-Throughput Nucleotide Sequencing, Humans, Lymphocyte Activation, Mutation, Prognosis, Sezary Syndrome, Signal Transduction, Skin Neoplasms, Survival Rate, T-Lymphocytes
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.

DOI10.1038/ng.3444
Alternate JournalNat. Genet.
PubMed ID26551670
PubMed Central IDPMC4829974
Grant ListP30 CA016672 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
5U54HG003273 / HG / NHGRI NIH HHS / United States
CA16672 / CA / NCI NIH HHS / United States