Opportunities for targeted therapies: trametinib as a therapeutic approach to canine oral squamous cell carcinomas
Data files
Oct 18, 2024 version files 8.31 MB
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COSCC_168_fingerprint.bed
1.01 KB
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COSCC_168_fingerprint.bim
5.44 KB
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COSCC_168_fingerprint.fam
638 B
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COSCC.bed
1.29 MB
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COSCC.bim
7.01 MB
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COSCC.fam
638 B
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README.md
3.70 KB
Abstract
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.
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 >30% and located >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/)
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 > 3%) and removing all SNPs with any missingness. This left a dataset of 22 samples genotyped at 215,079 SNPs.
- Peralta, Santiago; Katt, William; Balkman, Cheryl et al. (2024). Opportunities for targeted therapies: trametinib as a therapeutic approach to canine oral squamous cell carcinomas [Preprint]. Research Square Platform LLC. https://doi.org/10.21203/rs.3.rs-4289451/v1