Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2

Alexander Ungewickell, Aparna Bhaduri, Eon Rios, Jason Reuter, Carolyn S. Lee, Angela Mah, Ashley Zehnder, Robert Ohgami, Shashikant Kulkarni, Randall Armstrong, Wen Kai Weng, Dita Gratzinger, Mahkam Tavallaee, Alain Rook, Michael Snyder, Youn Kim, Paul A. Khavari

Research output: Contribution to journalArticlepeer-review

163 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1056-1060
Number of pages5
JournalNature genetics
Volume47
Issue number9
DOIs
StatePublished - Aug 27 2015
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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