The mutational landscape of cutaneous T cell lymphoma and Sézary syndrome

Ana Carolina Da Silva Almeida, Francesco Abate, Hossein Khiabanian, Estela Martinez-Escala, Joan Guitart, Cornelis P. Tensen, Maarten H. Vermeer, Raul Rabadan, Adolfo Ferrando, Teresa Palomero

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Sézary syndrome is a leukemic and aggressive form of cutaneous T cell lymphoma (CTCL) resulting from the malignant transformation of skin-homing central memory CD4+ T cells. Here we performed whole-exome sequencing of tumor-normal sample pairs from 25 patients with Sézary syndrome and 17 patients with other CTCLs. These analyses identified a distinctive pattern of somatic copy number alterations in Sézary syndrome, including highly prevalent chromosomal deletions involving the TP53, RB1, PTEN, DNMT3A and CDKN1B tumor suppressors. Mutation analysis identified a broad spectrum of somatic mutations in key genes involved in epigenetic regulation (TET2, CREBBP, KMT2D (MLL2), KMT2C (MLL3), BRD9, SMARCA4 and CHD3) and signaling, including MAPK1, BRAF, CARD11 and PRKG1 mutations driving increased MAPK, NF-κB and NFAT activity upon T cell receptor stimulation. Collectively, our findings provide new insights into the genetics of Sézary syndrome and CTCL and support the development of personalized therapies targeting key oncogenically activated signaling pathways for the treatment of these diseases.

Original languageEnglish (US)
Pages (from-to)1465-1470
Number of pages6
JournalNature Genetics
Volume47
Issue number12
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

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Cutaneous T-Cell Lymphoma
Mutation
Exome
T-Cell Antigen Receptor
Epigenomics
Neoplasms
T-Lymphocytes
Skin
Therapeutics
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Da Silva Almeida, A. C., Abate, F., Khiabanian, H., Martinez-Escala, E., Guitart, J., Tensen, C. P., ... Palomero, T. (2015). The mutational landscape of cutaneous T cell lymphoma and Sézary syndrome. Nature Genetics, 47(12), 1465-1470. https://doi.org/10.1038/ng.3442
Da Silva Almeida, Ana Carolina ; Abate, Francesco ; Khiabanian, Hossein ; Martinez-Escala, Estela ; Guitart, Joan ; Tensen, Cornelis P. ; Vermeer, Maarten H. ; Rabadan, Raul ; Ferrando, Adolfo ; Palomero, Teresa. / The mutational landscape of cutaneous T cell lymphoma and Sézary syndrome. In: Nature Genetics. 2015 ; Vol. 47, No. 12. pp. 1465-1470.
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Da Silva Almeida, AC, Abate, F, Khiabanian, H, Martinez-Escala, E, Guitart, J, Tensen, CP, Vermeer, MH, Rabadan, R, Ferrando, A & Palomero, T 2015, 'The mutational landscape of cutaneous T cell lymphoma and Sézary syndrome', Nature Genetics, vol. 47, no. 12, pp. 1465-1470. https://doi.org/10.1038/ng.3442

The mutational landscape of cutaneous T cell lymphoma and Sézary syndrome. / Da Silva Almeida, Ana Carolina; Abate, Francesco; Khiabanian, Hossein; Martinez-Escala, Estela; Guitart, Joan; Tensen, Cornelis P.; Vermeer, Maarten H.; Rabadan, Raul; Ferrando, Adolfo; Palomero, Teresa.

In: Nature Genetics, Vol. 47, No. 12, 01.12.2015, p. 1465-1470.

Research output: Contribution to journalArticle

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Da Silva Almeida AC, Abate F, Khiabanian H, Martinez-Escala E, Guitart J, Tensen CP et al. The mutational landscape of cutaneous T cell lymphoma and Sézary syndrome. Nature Genetics. 2015 Dec 1;47(12):1465-1470. https://doi.org/10.1038/ng.3442