Cosmic » Paper » Overview » Koo GC et al

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Reference

Janus Kinase 3-Activating Mutations Identified in Natural Killer/T-cell Lymphoma.

Paper Id
COSP29101
Authors
Koo GC,Tan SY,Tang T,Poon SL,Allen GE,Tan L,Chong SC,Ong WS,Tay K,Tao M,Quek R,Loong S,Yeoh KW,Yap SP,Lee KA,Lim LC,Tan D,Goh C,Cutcutache I,Yu W,Ng CC,Rajasegaran V,Heng HL,Gan A,Ong CK,Rozen S,Tan P,Teh BT and Lim ST
Affiliation
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.
Journal
Cancer discovery 2012
ISSN:2159-8290
PUBMED:22705984
Abstract
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
Curated
Genes Analysed
229
Mutated Samples
255
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Genes Samples CDS Mutation AA Mutation
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Non-Mutant Genes Gene Id (COSG)
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Non-Mutant Samples Sample Id (COSS)
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Sample Name Mutation Count
This tab shows non coding variant in the selected study/paper [more details]
Sample ID Sample Name ID NCV Annotation Zygosity Chromosome Genome start Genome stop Genome version Strand WT seq Mut seq