| Literature DB >> 26258847 |
Alexander Ungewickell1,2, Aparna Bhaduri1, Eon Rios1, Jason Reuter3, Carolyn S Lee1, Angela Mah1, Ashley Zehnder1, Robert Ohgami4, Shashikant Kulkarni5,6,7, Randall Armstrong8, Wen-Kai Weng8, Dita Gratzinger4, Mahkam Tavallaee9, Alain Rook10, Michael Snyder3, Youn Kim9, Paul A Khavari1,11.
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-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.Entities:
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Year: 2015 PMID： 26258847 PMCID： PMC6091217 DOI： 10.1038/ng.3370
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330