Comparative oncology DNA sequencing of canine T cell lymphoma via human hotspot panel
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J. Tyson McDonald1,*, Athena Kritharis2,*, Afshin Beheshti3, Monika Pilichowska4, Kristine Burgess5, Luisel Ricks-Santi1, Elizabeth McNiel5, Cheryl A. London5, Dashnamoorthy Ravi2 and Andrew M. Evens2
1Cancer Research Center, Hampton University, Hampton, VA, USA
2Division of Blood Disorders, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
3WYLE, NASA Ames Research Center, Moffett Field, CA, USA
4Division of Pathology, Tufts Medical Center, Boston, MA, USA
5Cummings School of Veterinary Medicine, Tufts University, Boston, MA, USA
*These authors contributed equally to this work
Andrew M. Evens, email: email@example.com
Keywords: canine; T cell lymphoma; DNA sequencing; cancer hotspots; Non-Hodgkin lymphoma
Received: February 08, 2018 Accepted: April 08, 2018 Published: April 27, 2018
T-cell lymphoma (TCL) is an uncommon and aggressive form of human cancer. Lymphoma is the most common hematopoietic tumor in canines (companion animals), with TCL representing approximately 30% of diagnoses. Collectively, the canine is an appealing model for cancer research given the spontaneous occurrence of cancer, intact immune system, and phytogenetic proximity to humans. We sought to establish mutational congruence of the canine with known human TCL mutations in order to identify potential actionable oncogenic pathways. Following pathologic confirmation, DNA was sequenced in 16 canine TCL (cTCL) cases using a custom Human Cancer Hotspot Panel of 68 genes commonly mutated in human TCL. Sequencing identified 4,527,638 total reads with average length of 229 bases containing 346 unique variants and 1,474 total variants; each sample had an average of 92 variants. Among these, there were 258 germline and 32 somatic variants. Among the 32 somatic variants there were 8 missense variants, 1 splice junction variant and the remaining were intron or synonymous variants. A frequency of 4 somatic mutations per sample were noted with >7 mutations detected in MET, KDR, STK11 and BRAF. Expression of these associated proteins were also detected via Western blot analyses. In addition, Sanger sequencing confirmed three variants of high quality (MYC, MET, and TP53 missense mutation). Taken together, the mutational spectrum and protein analyses showed mutations in signaling pathways similar to human TCL and also identified novel mutations that may serve as drug targets as well as potential biomarkers.
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