2. Academic Validation
  3. STAT3 Mutation Is Associated with STAT3 Activation in CD30+ ALK- ALCL

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

  • Cancers (Basel). 2020 Mar 16;12(3):702. doi: 10.3390/cancers12030702.
Emma I Andersson 1 2 3,  Oscar Brück 1 2,  Till Braun 4,  Susanna Mannisto 5,  Leena Saikko 6,  Sonja Lagström 7,  Pekka Ellonen 7,  Sirpa Leppä 5,  Marco Herling 4,  Panu E Kovanen 6,  Satu Mustjoki 1 2
Affiliations

Affiliations

  • 1 Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland.
  • 2 Translational Immunology Research program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland.
  • 3 HUSLAB, Laboratory of Genetics, Helsinki University Hospital, 00290 Helsinki, Finland.
  • 4 Department I of Internal Medicine, CMMC, CECAD, CIO-ABCD, University of Cologne, 50931 Cologne, Germany.
  • 5 Department of Oncology, Comprehensive Cancer Center, Helsinki University Hospital, 00290 Helsinki, Finland.
  • 6 Department of Pathology, HUSLAB, Helsinki University Central Hospital and University of Helsinki, 00290 Helsinki, Finland.
  • 7 Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014 Helsinki, Finland.
PMID: 32188095 DOI: 10.3390/cancers12030702
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.

Keywords

NGS; RHOA; STAT3; T-cells; lymphoma.

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