DOI: 10.5061/dryad.zs7h44jh9
title: Opportunities for targeted therapies: trametinib as a therapeutic approach to canine oral squamous cell carcinomas

description: Oral tumors are relatively common in dogs, and canine oral squamous cell
 carcinoma (COSCC) is the most prevalent oral malignancy of epithelial
 origin. COSCC is locally aggressive with up to 20% of patients showing
 regional or distant metastasis at the time of diagnosis. The treatment of
 choice depends on stage of progression and may include wide surgical
 excision, chemotherapy, radiation therapy or any combination thereof.
 Although long-term remission is possible, treatments are associated with
 significant morbidity and can negatively impact functionality and quality
 of life. As a result, many dog owners reject treatment entirely, and some
 patients are left with palliative care alone. OSCC tumors have significant
 upregulation of the RAS-RAF-MEK-MAPK signaling axis, and we had previously
 hypothesized that small-molecule inhibitors that target RAS signaling
 might effectively inhibit tumor growth and progression. Here, we
 demonstrate that the MEK inhibitor trametinib, an FDA-approved drug for
 human cancers, significantly blocks the growth of several aggressive COSCC
 cell lines derived from patient tumor samples. Given the limited treatment
 options currently available, and the high rate of owner rejection of these
 options, these findings provide new hope that more palatable treatment
 options may soon enter the veterinary clinic.
description: DNA from canine tumors, patient-derived xenograft (PDX) and cell
 lines was genotyped on the EMBARK version of the Illumina canineHD 220k
 bead array. Quality control included removing failed samples (missingness
 &gt; 3%) and removing all SNPs with any missingness. This left a
 dataset of 22 samples genotyped at 215,079 SNPs. 
description: # Opportunities for targeted therapies: trametinib as a therapeutic
 approach to canine oral squamous cell carcinomas Authors: William P. Katt,
 Cheryl E. Balkman, Scott D. Butler, Patrick C. Carney, Amy B.
 Todd-Donatto, Matthew E. Drozd, Gerald E. Duhamel, Nadine Fiani, Jordan C.
 Ford, Jennifer K. Grenier, Jessica J. Hayward, Kristiina Heikinheimo,
 Kelly R. Hume, Elizabeth S. Moore, Rishi Puri, Skylar R. Sylvester, Sydney
 L. Warshaw, Suzin M. Webb, Andrew C. White, Alexandra L. Wright, Richard
 A. Cerione, Santiago Peralta Dataset accessed on Dryad
 (doi:10.5061/dryad.zs7h44jh9) **DATA AND FILE OVERVIEW** 1\. Data
 description These data were generated to identify that the PDX and cell
 line samples are genetically related to their original canine tumor
 samples. DNA was extracted from the samples and genotyped on the CanineHD
 220k beadchip (Illumina Inc). Identifying information has not been
 included in this dataset. Two binary PLINK file datasets are included.
 PLINK is an open-source, free program commonly used for genotype data. The
 binary format includes three files: fam (sample information file), bim
 (variant information file), bed (biallelic genotype table). These are
 called using the command --bfile. Pre-filtering of these genotype files
 includes removing failed samples and all SNPs with any missingness. 2\.
 File List: **Dataset 1**. All raw data for the 22 samples included in the
 study. This dataset contains 215,079 SNPs. file name: COSCC.fam file
 description: text file containing information for each sample\ No header,
 6 fields: family ID within-family ID paternal ID ("0" if not in
 dataset) maternal ID ("0" if not in dataset) sex (1=male,
 2=female, 0=unknown) phenotype value (1=control, 2=case, -9=unknown) file
 name: COSCC.bim file description: text file containing information for
 each variant No header, 6 fields: chromosome code (1-38, 39=X, 40=Y,
 41=non-PAR X, 42=mitochondrial, 0=unknown) variant name genetic position,
 in morgans (or centimorgans) ("0" if unknown) position in
 base-pairs allele 1 (usually minor) allele 2 (usually major) file name:
 COSCC.bed \ file description: binary file containing genotypes for each
 sample [in the same order as the fam file] at each variant [in the same
 order as the bim file] **Dataset 2**. Genotype data for the 22 samples
 using the 168 SNP fingerprint only. The 168 SNPs were selected as
 described in the manuscript, including minor allele frequency &gt;30% and
 located &gt;10 Mb apart. This file has reference and alternate alleles
 that match the canFam3 reference genome. file name:
 COSCC_168_fingerprint.fam file description: text file containing
 information for each sample No header, 6 fields: family ID within-family
 ID paternal ID ("0" if not in dataset) maternal ID
 ("0" if not in dataset) sex (1=male, 2=female, 0=unknown)
 phenotype value (1=control, 2=case, -9=unknown) file name:
 COSCC_168_fingerprint.bim file description: text file containing
 information for each variant No header, 6 fields: chromosome code (1-38,
 39=X, 40=Y, 41=non-PAR X, 42=mitochondrial, 0=unknown) variant name
 genetic position, in morgans (or centimorgans) ("0" if unknown)\
 position in base-pairs allele 1 (alternate) allele 2 (reference) file
 name: COSCC_168_fingerprint.bed file description: binary file containing
 genotypes for each sample [in the same order as the fam file] at each
 variant [in the same order as the bim file] **METHODOLOGICAL INFORMATION**
 Genotypes were generated by Illumina Inc (San Diego, CA) through Embark
 Veterinary Inc. Raw data files were converted to PLINK format and quality
 control was performed in PLINK v 1.9
 ([https://www.cog-genomics.org/plink2/](https://www.cog-genomics.org/plink2/))