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Volume 10
Issue 7
10.3390/genes10070505
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Article

Activating Mutations in PTPN11 and KRAS in Canine Histiocytic Sarcomas

by
Marilia Takada
1,†, 1,
Tuddow Thaiwong
2,
Marlee Richter
1,
Sarah M. Corner
2, 1,
Matti Kiupel
2,3 and
Vilma Yuzbasiyan-Gurkan
1,*
1
Comparative Medicine and Integrative Biology Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA
2
Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Michigan State University, Lansing, MI 48910, USA
3
Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA
*
Author to whom correspondence should be addressed.
†
Dr. Takada’s current affiliation is: Department of Surgical Sciences, University of Wisconsin-Madison School of Veterinary Medicine, Madison, WI 53706, USA.
Genes 2019, 10(7), 505; https://doi.org/10.3390/genes10070505
Received: 26 April 2019 / Revised: 25 June 2019 / Accepted: 26 June 2019 / Published: 4 July 2019
(This article belongs to the Special Issue Canine Genetics)
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Abstract

While the genetic contributions to the predisposition of Bernese mountain dogs (BMDs) to histiocytic sarcoma (HS) remains unclear, some insights into key genetic drivers have been gained. Our group recently reported a mutation in the PTPN11 gene (E76K). We have now identified a second missense mutation in PTPN11 (G503V), and a mutation in KRAS (Q61H) present in HS cell lines. These mutations are associated with malignancies in humans, and known to be gain-of-function mutations that result in activation of the mitogen-activated protein kinase (MAPK) pathway. The goal of the present study was to evaluate the prevalence of these mutations in a large sample of HS cases from BMDs and golden retrievers, and in lymphoma cases, from a cohort of BMDs. Mutations in PTPN11 were present in HS in 41/96 (43%) BMDs, and in 3/13 (23%) golden retrievers. PTPN11 mutations E76K and G503V did not coexist in the same neoplasm. The KRAS mutation was much less frequent, with a prevalence of 3.1% (3/96). We did not identify either PTPN11 nor KRAS mutations in any of the lymphoma samples. These results point out the potential relevance of PTPN11 and KRAS mutations as activators of the oncogenic MAPK pathway for canine HS, particularly in BMDs. View Full-Text
Keywords: Bernese mountain dog; histiocytic sarcoma; PTPN11; KRAS; somatic mutation Bernese mountain dog; histiocytic sarcoma; PTPN11; KRAS; somatic mutation
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MDPI and ACS Style

Takada, M.; Smyth, L.A.; Thaiwong, T.; Richter, M.; Corner, S.M.; Schall, P.Z.; Kiupel, M.; Yuzbasiyan-Gurkan, V. Activating Mutations in PTPN11 and KRAS in Canine Histiocytic Sarcomas. Genes 2019, 10, 505. https://doi.org/10.3390/genes10070505

AMA Style

Takada M, Smyth LA, Thaiwong T, Richter M, Corner SM, Schall PZ, Kiupel M, Yuzbasiyan-Gurkan V. Activating Mutations in PTPN11 and KRAS in Canine Histiocytic Sarcomas. Genes. 2019; 10(7):505. https://doi.org/10.3390/genes10070505

Chicago/Turabian Style

Takada, Marilia, Lauren A. Smyth, Tuddow Thaiwong, Marlee Richter, Sarah M. Corner, Peter Z. Schall, Matti Kiupel, and Vilma Yuzbasiyan-Gurkan. 2019. "Activating Mutations in PTPN11 and KRAS in Canine Histiocytic Sarcomas" Genes 10, no. 7: 505. https://doi.org/10.3390/genes10070505

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