A novel recurrent NPM1-TYK2 gene fusion in cutaneous CD30-positive lymphoproliferative disorders

作者：Velusamy Thirunavukkarasu; Kiel Mark J; Sahasrabuddhe Anagh A; Rolland Delphine; Dixon Catherine A; Bailey Nathanael G; Betz Bryan L; Brown Noah A; Hristov Alexandra C; Wilcox Ryan A; Miranda Roberto N; Medeiros L Jeffrey; Jeon Yoon K; Inamdar Kedar V; Lim Megan S; Elenitoba Johnson Kojo S J^*

来源：Blood, 2014, 124(25): 3768-3771.

DOI：10.1182/blood-2014-07-588434

The spectrum of cutaneous CD30-positive lymphoproliferative disorders (LPDs) includes lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. Chromosomal translocations targeting tyrosine kinases in CD30-positive LPDs have not been described. Using whole-transcriptome sequencing, we identified a chimeric fusion involving NPM1 (5q35) and TYK2 (19p13) that encodes an NPM1-TYK2 protein containing the oligomerization domain of NPM1 and an intact catalytic domain in TYK2. Fluorescence in situ hybridization revealed NPM1-TYK2 fusions in 2 of 47 (4%) primary cases of CD30-positive LPDs and was absent in other mature T-cell neoplasms (n = 151). Functionally, NPM1-TYK2 induced constitutive TYK2, signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5 activation. Conversely, a kinase-defective NPM1-TYK2 mutant abrogated STAT1/3/5 signaling. Finally, short hairpin RNA-mediated silencing of TYK2 abrogated lymphoma cell growth. This is the first report of recurrent translocations involving TYK2, and it highlights the novel therapeutic opportunities in the treatment of CD30-positive LPDs with TYK2 translocations.

• 出版日期2014-12-11