The mutational landscape of cutaneous T cell lymphoma and Sezary syndrome
Menées respectivement sur 37 et 42 patients atteints d'un syndrome de Sézary ou d'un lymphome cutané des cellules T, ces deux études identifient un ensemble de mutations somatiques associées à diverses voies de signalisation
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 S
ézary syndrome and CTCL and support the development of personalized therapies targeting key oncogenically activated signaling pathways for the treatment of these diseases.
Nature Genetics , résumé, 2014