STAT3 Mutation Is Associated with STAT3 Activation in CD30(+) ALK(-) ALCL

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http://hdl.handle.net/10138/316186

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Andersson , E I , Brück , O , Braun , T , Mannisto , S , Saikko , L , Lagström , S , Ellonen , P , Leppä , S , Herling , M , Kovanen , P E & Mustjoki , S 2020 , ' STAT3 Mutation Is Associated with STAT3 Activation in CD30(+) ALK(-) ALCL ' , Cancers , vol. 12 , no. 3 , 702 . https://doi.org/10.3390/cancers12030702

Title: STAT3 Mutation Is Associated with STAT3 Activation in CD30(+) ALK(-) ALCL
Author: Andersson, Emma I.; Brück, Oscar; Braun, Till; Mannisto, Susanna; Saikko, Leena; Lagström, Sonja; Ellonen, Pekka; Leppä, Sirpa; Herling, Marco; Kovanen, Panu E.; Mustjoki, Satu
Contributor organization: Faculty of Medicine
HUSLAB
Hematologian yksikkö
University of Helsinki
Helsinki University Hospital Area
TRIMM - Translational Immunology Research Program
Department of Clinical Chemistry and Hematology
Research Programs Unit
HUS Comprehensive Cancer Center
Department of Oncology
Medicum
Institute for Molecular Medicine Finland
Department of Pathology
Date: 2020-03
Language: eng
Number of pages: 17
Belongs to series: Cancers
ISSN: 2072-6694
DOI: https://doi.org/10.3390/cancers12030702
URI: http://hdl.handle.net/10138/316186
Abstract: Peripheral T-cell lymphomas (PTCL) are a heterogeneous, and often aggressive group of non-Hodgkin lymphomas. Recent advances in the molecular and genetic characterization of PTCLs have helped to delineate differences and similarities between the various subtypes, and the JAK/STAT pathway has been found to play an important oncogenic role. Here, we aimed to characterize the JAK/STAT pathway in PTCL subtypes and investigate whether the activation of the pathway correlates with the frequency of STAT gene mutations. Patient samples from AITL (n = 30), ALCL (n = 21) and PTCL-NOS (n = 12) cases were sequenced for STAT3, STAT5B, JAK1, JAK3, and RHOA mutations using amplicon sequencing and stained immunohistochemically for pSTAT3, pMAPK, and pAKT. We discovered STAT3 mutations in 13% of AITL, 13% of ALK(+) ALCL, 38% of ALK ALCL and 17% of PTCL-NOS cases. However, no STAT5B mutations were found and JAK mutations were only present in ALK(-) ALCL (15%). Concurrent mutations were found in all subgroups except ALK(+) ALCL where STAT3 mutations were always seen alone. High pY-STAT3 expression was observed especially in AITL and ALCL samples. When studying JAK-STAT pathway mutations, pY-STAT3 expression was highest in PTCLs harboring either JAK1 or STAT3 mutations and CD30(+) phenotype representing primarily ALK ALCLs. Further investigation is needed to elucidate the molecular mechanisms of JAK-STAT pathway activation in PTCL.
Subject: lymphoma
T-cells
STAT3
RHOA
NGS
PERIPHERAL T-CELL
LYMPHOMA
KINASE
FREQUENT
TRANSPLANTATION
GEMCITABINE
SIGNATURES
LANDSCAPE
DIAGNOSIS
3122 Cancers
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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