Whole-genome sequencing reveals oncogenic mutations in mycosis fungoides

2015/06/17 by Laura Y. McGirt, Peilin Jia, Devin A. Baerenwald +9 · 27 citations
Medicine · #Cutaneous lymphoproliferative disorders research #Vascular Tumors and Angiosarcomas #Chronic Lymphocytic Leukemia Research

paper · pdf · doi:10.1182/blood-2014-11-611194

Abstract

The pathogenesis of mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is unknown. Although genetic alterations have been identified, none are considered consistently causative in MF. To identify potential drivers of MF, we performed whole-genome sequencing of MF tumors and matched normal skin. Targeted ultra-deep sequencing of MF samples and exome sequencing of CTCL cell lines were also performed. Multiple mutations were identified that affected the same pathways, including epigenetic, cell-fate regulation, and cytokine signaling, in MF tumors and CTCL cell lines. Specifically, interleukin-2 signaling pathway mutations, including activating Janus kinase 3 (JAK3) mutations, were detected. Treatment with a JAK3 inhibitor significantly reduced CTCL cell survival. Additionally, the mutation data identified 2 other potential contributing factors to MF, ultraviolet light, and a polymorphism in the tumor suppressor p53 (TP53). Therefore, genetic alterations in specific pathways in MF were identified that may be viable, effective new targets for treatment.

Citations

• Long-term Outcome of 525 Patients With Mycosis Fungoides and Sézary Syndrome

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