Please use this identifier to cite or link to this item:
https://doi.org/10.1038/leu.2016.13
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dc.title | JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma | |
dc.contributor.author | Nairismagi, M-L | |
dc.contributor.author | Tan, J | |
dc.contributor.author | Lim, JQ | |
dc.contributor.author | Nagarajan, S | |
dc.contributor.author | Ng, CCY | |
dc.contributor.author | Rajasegaran, V | |
dc.contributor.author | Huang, D | |
dc.contributor.author | Lim, WK | |
dc.contributor.author | Laurensia, Y | |
dc.contributor.author | Wijaya, GC | |
dc.contributor.author | Li, ZM | |
dc.contributor.author | Cutcutache, I | |
dc.contributor.author | Pang, WL | |
dc.contributor.author | Thangaraju, S | |
dc.contributor.author | Ha, J | |
dc.contributor.author | Khoo, LP | |
dc.contributor.author | Chin, ST | |
dc.contributor.author | Dey, S | |
dc.contributor.author | Poore, G | |
dc.contributor.author | Tan, LHC | |
dc.contributor.author | Koh, HKM | |
dc.contributor.author | Sabai, K | |
dc.contributor.author | Rao, H-L | |
dc.contributor.author | Chuah, KL | |
dc.contributor.author | Ho, Y-H | |
dc.contributor.author | Ng, S-B | |
dc.contributor.author | Chuang, S-S | |
dc.contributor.author | Zhang, F | |
dc.contributor.author | Liu, Y-H | |
dc.contributor.author | Pongpruttipan, T | |
dc.contributor.author | Ko, YH | |
dc.contributor.author | Cheah, P-L | |
dc.contributor.author | Karim, N | |
dc.contributor.author | Chng, W-J | |
dc.contributor.author | Tang, T | |
dc.contributor.author | Tao, M | |
dc.contributor.author | Tay, K | |
dc.contributor.author | Farid, M | |
dc.contributor.author | Quek, R | |
dc.contributor.author | Rozen, SG | |
dc.contributor.author | Tan, P | |
dc.contributor.author | Teh, BT | |
dc.contributor.author | Lim, ST | |
dc.contributor.author | Tan, S-Y | |
dc.contributor.author | Ong, CK | |
dc.date.accessioned | 2021-11-17T09:40:05Z | |
dc.date.available | 2021-11-17T09:40:05Z | |
dc.date.issued | 2016-06-01 | |
dc.identifier.citation | Nairismagi, 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.issn | 08876924 | |
dc.identifier.issn | 14765551 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/206601 | |
dc.description.abstract | Epitheliotropic 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.iso | en | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.source | Elements | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Oncology | |
dc.subject | Hematology | |
dc.subject | GAMMA-DELTA-T | |
dc.subject | INTEGRATIVE GENOMICS VIEWER | |
dc.subject | FOLLICULAR LYMPHOMA | |
dc.subject | ALPHA-SUBUNIT | |
dc.subject | MAP KINASE | |
dc.subject | MUTATIONS | |
dc.subject | CANCER | |
dc.subject | GENES | |
dc.subject | EXPRESSION | |
dc.subject | POPULATION | |
dc.type | Article | |
dc.date.updated | 2021-11-17T07:47:47Z | |
dc.contributor.department | DEPT OF PATHOLOGY | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1038/leu.2016.13 | |
dc.description.sourcetitle | LEUKEMIA | |
dc.description.volume | 30 | |
dc.description.issue | 6 | |
dc.description.page | 1311-1319 | |
dc.description.place | UNITED KINGDOM | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
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File | Description | Size | Format | Access Settings | Version | |
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Nairismagi ML. Leukemia 2016. JAK-STAT G-protein in MEITL.pdf | 3.3 MB | Adobe PDF | CLOSED | Published |
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