Megan L Ludwig1, Aditi Kulkarni2, Andrew C Birkeland2, Nicole L Michmerhuizen3, Susan K Foltin2, Jacqueline E Mann4, Rebecca C Hoesli2, Samantha N Devenport1, Brittany M Jewell2, Andrew G Shuman5, Matthew E Spector6, Thomas E Carey7, Hui Jiang8, J Chad Brenner9. 1. Department of Otolaryngology - Head and Neck Surgery, United States; Program in Cellular and Molecular Biology, United States. 2. Department of Otolaryngology - Head and Neck Surgery, United States. 3. Department of Otolaryngology - Head and Neck Surgery, United States; Department of Pharmacology, United States. 4. Department of Otolaryngology - Head and Neck Surgery, United States; Department of Pathology, United States. 5. Department of Otolaryngology - Head and Neck Surgery, United States; Center for Bioethics and Social Sciences in Medicine, United States; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI. University of Michigan Medical School, Ann Arbor, MI, United States. 6. Department of Otolaryngology - Head and Neck Surgery, United States; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI. University of Michigan Medical School, Ann Arbor, MI, United States. 7. Department of Otolaryngology - Head and Neck Surgery, United States; Department of Pharmacology, United States; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI. University of Michigan Medical School, Ann Arbor, MI, United States. 8. Department of Biostatistics, United States; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI. University of Michigan Medical School, Ann Arbor, MI, United States. 9. Department of Otolaryngology - Head and Neck Surgery, United States; Department of Pharmacology, United States; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI. University of Michigan Medical School, Ann Arbor, MI, United States. Electronic address: chadbren@umich.edu.
Abstract
OBJECTIVES: We sought to describe the genetic complexity of 14 UM-SCC oral cavity cancer cell lines that have remained uncharacterized despite being used as model systems for decades. MATERIALS AND METHODS: We performed exome sequencing on 14 oral cavity UM-SCC cell lines and denote the mutational profile of each line. We used a SNP array to profile the multiple copy number variations of each cell line and use immunoblotting to compare alterations to protein expression of commonly amplified genes (EGFR, PIK3CA, etc.). RNA sequencing was performed to characterize the expression of genes with copy number alterations. RESULTS: The cell lines displayed a highly complex network of genetic aberrations that was consistent with alterations identified in the HNSCC TCGA project including PIK3CA amplification, CDKN2A deletion, as well as TP53 and CASP8 mutations, enabling genetic stratification of each cell line in the panel. Copy number FISH and spectral karyotyping analysis demonstrate that cell lines retain chromosomal heterogeneity. CONCLUSIONS: Collectively, we developed an important resource for future oral cavity HNSCC cell line studies and highlight the complexity of genomic aberrations in cell lines.
OBJECTIVES: We sought to describe the genetic complexity of 14 UM-SCC oral cavity cancer cell lines that have remained uncharacterized despite being used as model systems for decades. MATERIALS AND METHODS: We performed exome sequencing on 14 oral cavity UM-SCC cell lines and denote the mutational profile of each line. We used a SNP array to profile the multiple copy number variations of each cell line and use immunoblotting to compare alterations to protein expression of commonly amplified genes (EGFR, PIK3CA, etc.). RNA sequencing was performed to characterize the expression of genes with copy number alterations. RESULTS: The cell lines displayed a highly complex network of genetic aberrations that was consistent with alterations identified in the HNSCC TCGA project including PIK3CA amplification, CDKN2A deletion, as well as TP53 and CASP8 mutations, enabling genetic stratification of each cell line in the panel. Copy number FISH and spectral karyotyping analysis demonstrate that cell lines retain chromosomal heterogeneity. CONCLUSIONS: Collectively, we developed an important resource for future oral cavity HNSCC cell line studies and highlight the complexity of genomic aberrations in cell lines.
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