Please use this identifier to cite or link to this item: https://doi.org/10.1038/leu.2016.13
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dc.titleJAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma
dc.contributor.authorNairismagi, M-L
dc.contributor.authorTan, J
dc.contributor.authorLim, JQ
dc.contributor.authorNagarajan, S
dc.contributor.authorNg, CCY
dc.contributor.authorRajasegaran, V
dc.contributor.authorHuang, D
dc.contributor.authorLim, WK
dc.contributor.authorLaurensia, Y
dc.contributor.authorWijaya, GC
dc.contributor.authorLi, ZM
dc.contributor.authorCutcutache, I
dc.contributor.authorPang, WL
dc.contributor.authorThangaraju, S
dc.contributor.authorHa, J
dc.contributor.authorKhoo, LP
dc.contributor.authorChin, ST
dc.contributor.authorDey, S
dc.contributor.authorPoore, G
dc.contributor.authorTan, LHC
dc.contributor.authorKoh, HKM
dc.contributor.authorSabai, K
dc.contributor.authorRao, H-L
dc.contributor.authorChuah, KL
dc.contributor.authorHo, Y-H
dc.contributor.authorNg, S-B
dc.contributor.authorChuang, S-S
dc.contributor.authorZhang, F
dc.contributor.authorLiu, Y-H
dc.contributor.authorPongpruttipan, T
dc.contributor.authorKo, YH
dc.contributor.authorCheah, P-L
dc.contributor.authorKarim, N
dc.contributor.authorChng, W-J
dc.contributor.authorTang, T
dc.contributor.authorTao, M
dc.contributor.authorTay, K
dc.contributor.authorFarid, M
dc.contributor.authorQuek, R
dc.contributor.authorRozen, SG
dc.contributor.authorTan, P
dc.contributor.authorTeh, BT
dc.contributor.authorLim, ST
dc.contributor.authorTan, S-Y
dc.contributor.authorOng, CK
dc.date.accessioned2021-11-17T09:40:05Z
dc.date.available2021-11-17T09:40:05Z
dc.date.issued2016-06-01
dc.identifier.citationNairismagi, M-L, Tan, J, Lim, JQ, Nagarajan, S, Ng, CCY, Rajasegaran, V, Huang, D, Lim, WK, Laurensia, Y, Wijaya, GC, Li, ZM, Cutcutache, I, Pang, WL, Thangaraju, S, Ha, J, Khoo, LP, Chin, ST, Dey, S, Poore, G, Tan, LHC, Koh, HKM, Sabai, K, Rao, H-L, Chuah, KL, Ho, Y-H, Ng, S-B, Chuang, S-S, Zhang, F, Liu, Y-H, Pongpruttipan, T, Ko, YH, Cheah, P-L, Karim, N, Chng, W-J, Tang, T, Tao, M, Tay, K, Farid, M, Quek, R, Rozen, SG, Tan, P, Teh, BT, Lim, ST, Tan, S-Y, Ong, CK (2016-06-01). JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma. LEUKEMIA 30 (6) : 1311-1319. ScholarBank@NUS Repository. https://doi.org/10.1038/leu.2016.13
dc.identifier.issn08876924
dc.identifier.issn14765551
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/206601
dc.description.abstractEpitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available .
dc.language.isoen
dc.publisherNATURE PUBLISHING GROUP
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectOncology
dc.subjectHematology
dc.subjectGAMMA-DELTA-T
dc.subjectINTEGRATIVE GENOMICS VIEWER
dc.subjectFOLLICULAR LYMPHOMA
dc.subjectALPHA-SUBUNIT
dc.subjectMAP KINASE
dc.subjectMUTATIONS
dc.subjectCANCER
dc.subjectGENES
dc.subjectEXPRESSION
dc.subjectPOPULATION
dc.typeArticle
dc.date.updated2021-11-17T07:47:47Z
dc.contributor.departmentDEPT OF PATHOLOGY
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1038/leu.2016.13
dc.description.sourcetitleLEUKEMIA
dc.description.volume30
dc.description.issue6
dc.description.page1311-1319
dc.description.placeUNITED KINGDOM
dc.published.statePublished
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