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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

197 Scopus citations

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

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'The mutational landscape of cutaneous T cell lymphoma and Sézary syndrome'. Together they form a unique fingerprint.

Cite this