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Blood. 2015 Jul 23;126(4):508-19. doi: 10.1182/blood-2014-11-611194. Epub 2015 Jun 16.

Whole-genome sequencing reveals oncogenic mutations in mycosis fungoides.

Author information

1
Department of Hematology/Oncology, Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC; and Department of Medicine/Division of Dermatology.
2
Department of Biomedical Informatics, Center for Quantitative Sciences.
3
Department of Medicine/Division of Dermatology.
4
Department of Pathology, Microbiology and Immunology.
5
Vanderbilt-Ingram Cancer Center, Department of Cancer Biology.
6
Vanderbilt-Ingram Cancer Center.
7
Department of Medicine/Division of Hematology-Oncology, Tennessee Valley Healthcare System, and.
8
Department of Biomedical Informatics, Center for Quantitative Sciences, Department of Cancer Biology, Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN.

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.

PMID:
26082451
PMCID:
PMC4513251
DOI:
10.1182/blood-2014-11-611194
[Indexed for MEDLINE]
Free PMC Article

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