Whole-genome sequencing reveals oncogenic mutations in mycosis fungoides.

McGirt LY, Jia P, Baerenwald DA, Duszynski RJ, Dahlman KB, Zic JA, Zwerner JP, Hucks D, Dave U, Zhao Z, Eischen CM
Blood. 2015 126 (4): 508-19

PMID: 26082451 · PMCID: PMC4513251 · DOI:10.1182/blood-2014-11-611194

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.

© 2015 by The American Society of Hematology.

MeSH Terms (17)

Adult Aged Exome Female Follow-Up Studies Genome, Human High-Throughput Nucleotide Sequencing Humans Male Middle Aged Mutation Mycosis Fungoides Oncogenes Retrospective Studies Sequence Analysis, DNA Skin Neoplasms Ultraviolet Rays

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