Universität zu Köln

Andersson, Emma I., Bruck, Oscar, Braun, Till, Mannisto, Susanna, Saikko, Leena, Lagstrom, Sonja, Ellonen, Pekka ORCID: 0000-0001-6072-0489, Leppa, Sirpa ORCID: 0000-0002-8265-511X, Herling, Marco, Kovanen, Panu E. and Mustjoki, Satu ORCID: 0000-0002-0816-8241 (2020). STAT3 Mutation Is Associated with STAT3 Activation in CD30(+) ALK(-) ALCL. Cancers, 12 (3). BASEL: MDPI. ISSN 2072-6694

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Andersson, Emma I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruck, Oscar UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, Till UNSPECIFIED UNSPECIFIED UNSPECIFIED Mannisto, Susanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Saikko, Leena UNSPECIFIED UNSPECIFIED UNSPECIFIED Lagstrom, Sonja UNSPECIFIED UNSPECIFIED UNSPECIFIED Ellonen, Pekka UNSPECIFIED orcid.org/0000-0001-6072-0489 UNSPECIFIED Leppa, Sirpa UNSPECIFIED orcid.org/0000-0002-8265-511X UNSPECIFIED Herling, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Kovanen, Panu E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mustjoki, Satu UNSPECIFIED orcid.org/0000-0002-0816-8241 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-341995
DOI:	10.3390/cancers12030702
Journal or Publication Title:	Cancers
Volume:	12
Number:	3
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PERIPHERAL T-CELL; LYMPHOMA; KINASE; FREQUENT; RHOA; TRANSPLANTATION; GEMCITABINE; SIGNATURES; LANDSCAPE; DIAGNOSIS Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34199