A Recurrent <i>STAT5B<sup>N642H</sup></i> Driver Mutation in Feline Alimentary T Cell Lymphoma
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 experim...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/20/5238 |
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| author | Matthias Kieslinger Alexander Swoboda Nina Kramer Patricia Freund Barbara Pratscher Heidi A. Neubauer Ralf Steinborn Birgitt Wolfesberger Andrea Fuchs-Baumgartinger Richard Moriggl Iwan A. Burgener |
| author_facet | Matthias Kieslinger Alexander Swoboda Nina Kramer Patricia Freund Barbara Pratscher Heidi A. Neubauer Ralf Steinborn Birgitt Wolfesberger Andrea Fuchs-Baumgartinger Richard Moriggl Iwan A. Burgener |
| author_sort | Matthias Kieslinger |
| collection | DOAJ |
| description | 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 <i>STAT3</i> or <i>STAT5B</i> identifies the presence of the <i>STAT5B<sup>N642H</sup></i> 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 <i>STAT5B</i> 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. |
| first_indexed | 2024-03-10T06:40:21Z |
| format | Article |
| id | doaj.art-49c2188e86494c799440ea417829c80c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T06:40:21Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-49c2188e86494c799440ea417829c80c2023-11-22T17:42:31ZengMDPI AGCancers2072-66942021-10-011320523810.3390/cancers13205238A Recurrent <i>STAT5B<sup>N642H</sup></i> Driver Mutation in Feline Alimentary T Cell LymphomaMatthias Kieslinger0Alexander Swoboda1Nina Kramer2Patricia Freund3Barbara Pratscher4Heidi A. Neubauer5Ralf Steinborn6Birgitt Wolfesberger7Andrea Fuchs-Baumgartinger8Richard Moriggl9Iwan A. Burgener10Department for Companion Animals and Horses, Division of Small Animal Internal Medicine, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaDepartment for Companion Animals and Horses, Division of Small Animal Internal Medicine, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaDepartment for Companion Animals and Horses, Division of Small Animal Internal Medicine, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaDepartment for Companion Animals and Horses, Division of Small Animal Internal Medicine, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaDepartment for Companion Animals and Horses, Division of Small Animal Internal Medicine, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaDepartment of Biomedical Sciences, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaGenomics Core Facility, VetCore, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaDepartment for Companion Animals and Horses, Division of Small Animal Internal Medicine, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaDepartment of Pathobiology, Institute of Pathology, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaDepartment of Biomedical Sciences, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaDepartment for Companion Animals and Horses, Division of Small Animal Internal Medicine, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaAlimentary 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 <i>STAT3</i> or <i>STAT5B</i> identifies the presence of the <i>STAT5B<sup>N642H</sup></i> 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 <i>STAT5B</i> 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.https://www.mdpi.com/2072-6694/13/20/5238STAT5Bdriver mutationfeline alimentary lymphomaSTAT3 |
| spellingShingle | Matthias Kieslinger Alexander Swoboda Nina Kramer Patricia Freund Barbara Pratscher Heidi A. Neubauer Ralf Steinborn Birgitt Wolfesberger Andrea Fuchs-Baumgartinger Richard Moriggl Iwan A. Burgener A Recurrent <i>STAT5B<sup>N642H</sup></i> Driver Mutation in Feline Alimentary T Cell Lymphoma Cancers STAT5B driver mutation feline alimentary lymphoma STAT3 |
| title | A Recurrent <i>STAT5B<sup>N642H</sup></i> Driver Mutation in Feline Alimentary T Cell Lymphoma |
| title_full | A Recurrent <i>STAT5B<sup>N642H</sup></i> Driver Mutation in Feline Alimentary T Cell Lymphoma |
| title_fullStr | A Recurrent <i>STAT5B<sup>N642H</sup></i> Driver Mutation in Feline Alimentary T Cell Lymphoma |
| title_full_unstemmed | A Recurrent <i>STAT5B<sup>N642H</sup></i> Driver Mutation in Feline Alimentary T Cell Lymphoma |
| title_short | A Recurrent <i>STAT5B<sup>N642H</sup></i> Driver Mutation in Feline Alimentary T Cell Lymphoma |
| title_sort | recurrent i stat5b sup n642h sup i driver mutation in feline alimentary t cell lymphoma |
| topic | STAT5B driver mutation feline alimentary lymphoma STAT3 |
| url | https://www.mdpi.com/2072-6694/13/20/5238 |
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