A Recurrent STAT5BN642H Driver Mutation in Feline Alimentary T Cell Lymphoma

Department for Companion Animals and Horses, Division of Small Animal Internal Medicine, University of Veterinary Medicine Vienna, 1210 Vienna, Austria

Department of Biomedical Sciences, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria

Genomics Core Facility, VetCore, University of Veterinary Medicine Vienna, 1210 Vienna, Austria

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Department of Pathobiology, Institute of Pathology, University of Veterinary Medicine Vienna, 1210 Vienna, Austria

Author to whom correspondence should be addressed.

Academic Editor: Andrew J. Brooks

Cancers 2021, 13(20), 5238; https://doi.org/10.3390/cancers13205238

Received: 17 September 2021 / Accepted: 5 October 2021 / Published: 19 October 2021

(This article belongs to the Special Issue Feature Paper from Journal Reviewers)

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Human gastrointestinal lymphomas are rare diseases with an incidence of one per 1,000,000 inhabitants per year. This paucity poses a major challenge in unravelling their underlying mechanism. In comparison, lymphoma is the most common malignancy in domestic cats and the gastrointestinal (GI) tract is the most common location for this disease. Here, we identify the driver mutation STAT5B^N642H in feline alimentary lymphoma, thereby establishing felines as a potential new model for a rare and incurable human T cell disease.

Abstract

Alimentary lymphomas arising from T cells are rare and aggressive malignancies in humans. In comparison, they represent the most common anatomical form of lymphoma in cats. Due to the low prevalence in humans, the underlying pathomechanism for these diseases is poorly characterised, limiting experimental analysis and therapeutic exploration. To date, activating mutations of the JAK/STAT core cancer pathway and particularly the STAT5B oncoprotein have been identified in human enteropathy-associated T cell lymphoma. Here, we describe a high homology of human and feline STAT3 and STAT5B proteins and strong conservation at the genomic level. Analysis of 42 samples of feline T cell alimentary lymphoma reveals broad activation of STAT3 and STAT5B. Screening for known activating mutations in STAT3 or STAT5B identifies the presence of the STAT5B^N642H driver mutation in feline enteropathy-associated T cell lymphoma in 7 out of 42 (16.67%) samples in total. Regarding lymphoma subtypes, the majority of mutations with 5 out of 17 (29.41%) cases were found in feline enteropathy-associated lymphoma type II (EATL II). This identification of an oncogenic STAT5B driver mutation in felines recapitulates the genetic situation in the corresponding human disease, thereby establishing the cat as a potential new model for a rare and incurable human T cell disease. View Full-Text

Keywords: STAT5B; driver mutation; feline alimentary lymphoma; STAT3

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MDPI and ACS Style

Kieslinger, M.; Swoboda, A.; Kramer, N.; Freund, P.; Pratscher, B.; Neubauer, H.A.; Steinborn, R.; Wolfesberger, B.; Fuchs-Baumgartinger, A.; Moriggl, R.; Burgener, I.A. A Recurrent STAT5B^N642H Driver Mutation in Feline Alimentary T Cell Lymphoma. Cancers 2021, 13, 5238. https://doi.org/10.3390/cancers13205238

AMA Style

Kieslinger M, Swoboda A, Kramer N, Freund P, Pratscher B, Neubauer HA, Steinborn R, Wolfesberger B, Fuchs-Baumgartinger A, Moriggl R, Burgener IA. A Recurrent STAT5B^N642H Driver Mutation in Feline Alimentary T Cell Lymphoma. Cancers. 2021; 13(20):5238. https://doi.org/10.3390/cancers13205238

Chicago/Turabian Style

Kieslinger, Matthias, Alexander Swoboda, Nina Kramer, Patricia Freund, Barbara Pratscher, Heidi A. Neubauer, Ralf Steinborn, Birgitt Wolfesberger, Andrea Fuchs-Baumgartinger, Richard Moriggl, and Iwan A. Burgener. 2021. "A Recurrent STAT5B^N642H Driver Mutation in Feline Alimentary T Cell Lymphoma" Cancers 13, no. 20: 5238. https://doi.org/10.3390/cancers13205238

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A Recurrent STAT5B^N642H Driver Mutation in Feline Alimentary T Cell Lymphoma

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