Identification of Gene Mutations and Fusion Genes in Patients with Sezary Syndrome
Por:
Prasad, A, Rabionet, R, Espinet, B, Zapata, L, Puiggros, A, Melero, C, Puig, A, Sarria-Trujillo, Y, Ossowski, S, Garcia-Muret, MP, Estrach, T, Servitje, O, Lopez-Lerma, I, Gallardo, F, Pujol, RM, Estivill, X
Publicada:
1 jul 2016
Resumen:
Sezary 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 Sezary cells, 14 of them fulfilling the diagnostic criteria of Sezary syndrome. We have discovered genes that could be involved in the pathogenesis of Sezary 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 Sezary 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.
Filiaciones:
Prasad, A:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain
UPF, Barcelona, Spain
CIBER Epidemiol & Publ Hlth CIBERESP, Barcelona, Spain
Hosp del Mar Med Res Inst IMIM, Barcelona, Spain
Rabionet, R:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain
UPF, Barcelona, Spain
CIBER Epidemiol & Publ Hlth CIBERESP, Barcelona, Spain
Hosp del Mar Med Res Inst IMIM, Barcelona, Spain
Espinet, B:
Hosp del Mar Med Res Inst IMIM, Barcelona, Spain
Hosp del Mar, Lab Mol Cytogenet, Pathol Serv, Barcelona, Spain
Zapata, L:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain
UPF, Barcelona, Spain
CIBER Epidemiol & Publ Hlth CIBERESP, Barcelona, Spain
Puiggros, A:
Hosp del Mar Med Res Inst IMIM, Barcelona, Spain
Hosp del Mar, Lab Mol Cytogenet, Pathol Serv, Barcelona, Spain
Melero, C:
Hosp del Mar Med Res Inst IMIM, Barcelona, Spain
Hosp del Mar, Lab Mol Cytogenet, Pathol Serv, Barcelona, Spain
Puig, A:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain
UPF, Barcelona, Spain
CIBER Epidemiol & Publ Hlth CIBERESP, Barcelona, Spain
Hosp del Mar Med Res Inst IMIM, Barcelona, Spain
Sarria-Trujillo, Y:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain
UPF, Barcelona, Spain
CIBER Epidemiol & Publ Hlth CIBERESP, Barcelona, Spain
Hosp del Mar Med Res Inst IMIM, Barcelona, Spain
Ossowski, S:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain
UPF, Barcelona, Spain
CIBER Epidemiol & Publ Hlth CIBERESP, Barcelona, Spain
Garcia-Muret, MP:
Hosp Santa Creu & Sant Pau, Dermatol Serv, Barcelona, Spain
Estrach, T:
Hosp Clin Barcelona, Dept Dermatol, Barcelona, Spain
Servitje, O:
Bellvitge Hosp, Dermatol Serv, Barcelona, Spain
Lopez-Lerma, I:
Hosp Valle De Hebron, Dept Dermatol, Barcelona, Spain
Gallardo, F:
Hosp del Mar Med Res Inst IMIM, Barcelona, Spain
Hosp del Mar, Dermatol Serv, Barcelona, Spain
Pujol, RM:
Hosp del Mar Med Res Inst IMIM, Barcelona, Spain
Hosp del Mar, Dermatol Serv, Barcelona, Spain
Estivill, X:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain
UPF, Barcelona, Spain
CIBER Epidemiol & Publ Hlth CIBERESP, Barcelona, Spain
Hosp del Mar Med Res Inst IMIM, Barcelona, Spain
Sidra Med & Res Ctr, Expt Genet, Doha, Qatar
Green Published, Hybrid Gold
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