Simple jQuery Dropdowns
Please use this identifier to cite or link to this item:
Title: JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma
Authors: M. L. Nairismägi
J. Tan
J. Q. Lim
S. Nagarajan
C. C.Y. Ng
V. Rajasegaran
D. Huang
W. K. Lim
Y. Laurensia
G. C. Wijaya
Z. M. Li
I. Cutcutache
W. L. Pang
S. Thangaraju
J. Ha
L. P. Khoo
S. T. Chin
S. Dey
G. Poore
L. H.C. Tan
H. K.M. Koh
K. Sabai
H. L. Rao
K. L. Chuah
Y. H. Ho
S. B. Ng
S. S. Chuang
F. Zhang
Y. H. Liu
T. Pongpruttipan
Y. H. Ko
P. L. Cheah
N. Karim
W. J. Chng
T. Tang
M. Tao
K. Tay
M. Farid
R. Quek
S. G. Rozen
P. Tan
B. T. Teh
S. T. Lim
S. Y. Tan
C. K. Ong
National Cancer Centre, Singapore
Duke-NUS Medical School Singapore
Cancer Science Institute of Singapore
Duke University
Singapore General Hospital
Singapore Health Services
Sun Yat-Sen University Cancer Center
Tan Tock Seng Hospital
Yong Loo Lin School of Medicine
Chi Mei Medical Center
Taipei Medical University
Guangdong General Hospital
Mahidol University
SungKyunKwan University, School of Medicine
University of Malaya
Hospital Raja Permaisuri Bainun
National University Hospital, Singapore
A-Star, Genome Institute of Singapore
A-Star, Institute of Molecular and Cell Biology
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jun-2016
Citation: Leukemia. Vol.30, No.6 (2016), 1311-1319
Abstract: © 2016 Macmillan Publishers Limited. 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 .
ISSN: 14765551
Appears in Collections:Scopus 2016-2017

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.