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

Aparna Prasad, Raquel Rabionet, Blanca Espinet, Luis Zapata, Anna Puiggros, Carme Melero, Anna Puig, Yaris Sarria-Trujillo, Stephan Ossowski, Maria P. Garcia-Muret, Teresa Estrach, Octavio Servitje, Ingrid Lopez-Lerma, Fernando Gallardo, Ramon M. Pujol, Xavier P. Estivill

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22 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1490-1499
Number of pages10
JournalJournal of Investigative Dermatology
Issue number7
Publication statusPublished - 1 Jul 2016


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Prasad, A., Rabionet, R., Espinet, B., Zapata, L., Puiggros, A., Melero, C., Puig, A., Sarria-Trujillo, Y., Ossowski, S., Garcia-Muret, M. P., Estrach, T., Servitje, O., Lopez-Lerma, I., Gallardo, F., Pujol, R. M., & Estivill, X. P. (2016). Identification of Gene Mutations and Fusion Genes in Patients with Sézary Syndrome. Journal of Investigative Dermatology, 136(7), 1490-1499.