Please use this identifier to cite or link to this item:
|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|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Apr 15, 2019
WEB OF SCIENCETM
checked on Apr 15, 2019
checked on Apr 7, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.