Comparative oncology DNA sequencing of canine T cell lymphoma via human hotspot panel

J. Tyson McDonald, Athena Kritharis, Afshin Beheshti, Monika Pilichowska, Kristine Burgess, Luisel Ricks-Santi, Elizabeth McNiel, Cheryl B. London, Dashnamoorthy Ravi, Andrew M. Evens

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)22693-22702
Number of pages10
JournalOncotarget
Volume9
Issue number32
DOIs
StatePublished - Apr 27 2018

All Science Journal Classification (ASJC) codes

  • Oncology

Keywords

  • Cancer hotspots
  • Canine
  • DNA sequencing
  • Non-Hodgkin lymphoma
  • T cell lymphoma

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