Name of Student:
Christopher Dickman
Research Supervisor: Dr. Cathie Garnis
Title of Presentation: Molecular Analysis of Cultured Normal and Dysplastic Cell Lines Modeling
Oral Cancer
Abstract
Background: Oral cancer is the 6th most commonly diagnosed cancer worldwide. Those
diagnosed with oral malignancy suffer from poor survival rates that have not improved in
decades. A better understanding of the molecular mechanisms governing disease initiation and
progression is required to improve this dismal statistic. Cell lines are invaluable model systems
for the investigation of cancer. Knowledge of the molecular alterations that exist within cell
models is needed to define the mechanisms governing cellular phenotypes. Several head and
neck cancer cell lines are commercially available and have been well characterized, however
very few normal and premalignant oral cell lines exist. Our objective was to molecularly
characterize a panel of novel immortalized oral cell lines derived from normal, non-malignant
tissues and dysplastic tissues. Ultimately, these cell lines and high throughput datasets
characterizing these lines will have great utility for modeling oral cancer progression – and
delineating the molecular drivers of this process.
Methods: Six immortalized normal cell lines oral (OKF4/TERT-1, OKF4/E6E7,
OKF6/TERT-1, OKF6/TERT-2, OKF6/E6E7, OKP7/bmi1/TERT) and two oral dysplasia lines
(DOK, POE9n/TERT) were analyzed for DNA copy number, mRNA expression, and
microRNA expression changes using tiling-path DNA microarrays, Agilent Whole Human
Genome Oligoarrays, and Exiqon’s miRCURY LNA Universal RT miRNA PCR system,
respectively. All data were compared to normal and dysplastic fresh frozen microdissected
tissues to determine how closely these models resembled clinical disease.
Results: Integrated analysis of our high resolution genetic and gene expression datasets
revealed the molecular landscape of each cell line. Both recurrent and distinct alteration events
were noted between dysplastic cell lines and through comparison against similar data from
clinical dysplasia tissues. Molecular results for individual cell lines and across all samples
have been summarized and made available for easy reference.
Conclusion/Significance: Cell lines derived from invasive tumors can harbor significant
genomic complexity. Evaluating suspected cancer-driving genes can be problematic against
this complicated background. This makes cell models of normal or premalignant tissues –
which typically harbor less molecular complexity – particularly valuable for modeling the
emergence of cancer phenotypes. By characterizing molecular dysregulation at multiple levels
in these cell models, we have created a valuable resource we can leverage for ongoing studies
assessing the impact of individual gene products and small RNA species on oral cancer
progression.