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|Title:||Janus kinase 3-activating mutations identifi ed in natural killer/T-cell lymphoma||Authors:||Koo, G.C.
|Issue Date:||2012||Citation:||Koo, G.C., Tan, S.Y., Tang, T., Poon, S.L., Allen, G.E., Tan, L., Chong, S.C., Ong, W.S., Tay, K., Tao, M., Quek, R., Loong, S., Yeoh, K.-W., Yap, S.P., Lee, K.A., Lim, L.C., Tan, D., Goh, C., Cutcutache, I., Yu, W., Ng, C.C.Y., Rajasegaran, V., Heng, H.L., Gan, A., Ong, C.K., Rozen, S., Tan, P., Teh, B.T., Lim, S.T. (2012). Janus kinase 3-activating mutations identifi ed in natural killer/T-cell lymphoma. Cancer Discovery 2 (7) : 591-597. ScholarBank@NUS Repository. https://doi.org/10.1158/2159-8290.CD-12-0028||Abstract:||The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identifi ed Janus kinase 3 (JAK3) somatic-activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Further validation of the prevalence of JAK3 mutations 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 JAK3 mutations. Functional characterization of the JAK3 mutations 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. SIGNIFICANCE: Gene mutations causing NKTCL have not been fully identifi ed. Through exome sequencing, we identifi ed activating mutations of JAK3 that may play a signifi cant role in the pathogenesis of NKTCLs. Our fi ndings have important implications for the management of patients with NKTCLs. © 2012 American Association for Cancer Research.||Source Title:||Cancer Discovery||URI:||http://scholarbank.nus.edu.sg/handle/10635/43098||ISSN:||21598274||DOI:||10.1158/2159-8290.CD-12-0028|
|Appears in Collections:||Staff Publications|
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