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

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...

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Authors: Prasad, Aparna|||0000-0002-6786-2313, Rabionet, Raquel|||0000-0001-5006-8140, Espinet Solà, Blanca|||0000-0002-4294-8145, Zapata Fenor, Luis|||0000-0003-4829-8363, Puiggros, Anna|||0000-0001-9627-4978, Melero, Carme, Puig, Anna, Sarria-Trujillo, Yaris|||0000-0003-2667-4372, Ossowski, Stephan|||0000-0002-7416-9568, Garcia Muret, Maria Pilar|||0000-0003-1714-5815, Estrach, Teresa|||0000-0002-4601-2811, Servitje, Octavio|||0000-0002-9910-9617, Lopez-Lerma, Ingrid|||0000-0002-7690-8926, Gallardo, Fernando|||0000-0002-8996-3828, Pujol Vallverdú, Ramón M.|||0000-0002-5622-6055, Estivill, Xavier|||0000-0002-0723-2256
Format: article
Publication Date:2016
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:289629
Online Access:https://ddd.uab.cat/record/289629
https://dx.doi.org/urn:doi:10.1016/j.jid.2016.03.024
Access Level:Open access
Description
Summary: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.

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