This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.
- Janus Kinase 3-Activating Mutations Identified in Natural Killer/T-cell Lymphoma.
- Paper ID
- 1NCCS-VARI Translational Research Laboratory, Department of Medical Sciences, 2Division of Clinical Trials and Epidemiological Sciences, Departments of 3Medical Oncology and 4Radiation Oncology, National Cancer Centre Singapore; Departments of 5Pathology, 6Hematology, and 7Ear, Nose and Throat, Singapore General Hospital; 8Neuroscience and Behavioral Disorders, 9Cancer and Stem Cell Biology Program, 10Duke-NUS Graduate Medical School Singapore, 11Cancer Science Institute of Singapore, NUS, and 12Genome Institute of Singapore, Singapore.
Cancer discovery, 2012
PMID: 22705984 (view at PubMed or Europe PMC)
- The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identified Janus kinase 3(JAK3) somatic-activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Further validation of the prevalence of JAK3mutations was determined by Sanger sequencing and high-resolution melt (HRM) analysis in an additional 61 cases. In total, 23 of 65 (35.4%) cases harbored JAK3mutations. Functional characterization of the JAK3mutations support its involvement in cytokine-independent JAK/STAT constitutive activation leading to increased cell growth. Moreover, treatment of both JAK3-mutant and wild-type NKTCL cell lines with a novel pan-JAK inhibitor, CP-690550, resulted in dose-dependent reduction of phosphorylated STAT5, reduced cell viability, and increased apoptosis. Hence, targeting the deregulated JAK/STAT pathway could be a promising therapy for patients with NKTCLs.
- Paper Status