Genomic analysis of mycosis fungoides and Sezary syndrome identifies recurrent alterations in TNFR2 NATURE GENETICS Ungewickell, A., Bhaduri, A., Rios, E., Reuter, J., Lee, C. S., Mah, A., Zehnder, A., Ohgami, R., Kulkarni, S., Armstrong, R., Weng, W., Gratzinger, D., Tavallaee, M., Rook, A., Snyder, M., Kim, Y., Khavari, P. A. 2015; 47 (9): 1056-?

Abstract

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 characterized. 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-?B 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.

View details for DOI 10.1038/ng.3370

View details for Web of Science ID 000360394100016