Genomic analysis of mycosis fungoides and Sezary syndrome identifies recurrent alterations in TNFR2
A partir de lignées cellulaires et d'échantillons tumoraux prélevés sur des patients atteints d'un lymphome T cutané (mycose fungoïde ou syndrome de Sézary), cette étude met en évidence la présence de mutations du gène codant le récepteur TNFR2 dans les tumeurs de 18% des patients
Mycosis fungoides and Sézary syndrome comprise the majority of cutaneous T cell lymphomas (CTCLs), disorders notable for their clinical heterogeneity that can present in skin or peripheral blood. Effective treatment options for CTCL are limited, and the genetic basis of these T cell lymphomas remains incompletely characterized1. Here we report recurrent point mutations and genomic gains of TNFRSF1B, encoding the tumor necrosis factor receptor TNFR2, in 18% of patients with mycosis fungoides and Sézary syndrome. Expression of the recurrent TNFR2 Thr377Ile mutant in T cells leads to enhanced non-canonical NF-
κB signaling that is sensitive to the proteasome inhibitor bortezomib. Using an integrative genomic approach, we additionally discovered a recurrent CTLA4-CD28 fusion, as well as mutations in downstream signaling mediators of these receptors.