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J Invest Dermatol. 2016 Jul;136(7):1490-1499. doi: 10.1016/j.jid.2016.03.024. Epub 2016 Mar 30.

Identification of Gene Mutations and Fusion Genes in Patients with Sézary Syndrome.

Author information

1
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
2
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Laboratory of Molecular Cytogenetics, Pathology Service, Hospital del Mar, Barcelona, Spain.
3
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Barcelona, Spain.
4
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
5
Dermatology Service, Hospital del Sant Pau, Barcelona, Spain.
6
Department of Dermatology, Hospital Clinic, Barcelona, Spain.
7
Dermatology Service, Hospital de Bellvitge, Barcelona, Spain.
8
Department of Dermatology, Hospital Vall d'Hebron, Barcelona, Spain.
9
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Dermatology Service, Hospital del Mar, Barcelona, Spain.
10
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Experimental Genetics, Sidra Medical and Research Centre, Doha, Qatar. Electronic address: xavier.estivill@crg.eu.

Abstract

Sézary syndrome is a leukemic form of cutaneous T-cell lymphoma with an aggressive clinical course. The genetic etiology of the disease is poorly understood, with chromosomal abnormalities and mutations in some genes being involved in the disease. The goal of our study was to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sézary cells, 14 of them fulfilling the diagnostic criteria of Sézary syndrome. We have discovered genes that could be involved in the pathogenesis of Sézary syndrome. Some of the genes that are affected by somatic point mutations include ITPR1, ITPR2, DSC1, RIPK2, IL6, and RAG2, with some of them mutated in more than one patient. We observed several somatic copy number variations shared between patients, including deletions and duplications of large segments of chromosome 17. Genes with potential function in the T-cell receptor signaling pathway and tumorigenesis were disrupted in Sézary syndrome patients, for example, CBLB, RASA2, BCL7C, RAMP3, TBRG4, and DAD1. Furthermore, we discovered several fusion events of interest involving RASA2, NFKB2, BCR, FASN, ZEB1, TYK2, and SGMS1. Our work has implications for the development of potential therapeutic approaches for this aggressive disease.

PMID:
27039262
DOI:
10.1016/j.jid.2016.03.024
[Indexed for MEDLINE]
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