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High-Performance Computing Predicts Double Minute Chromosomes in Cancer Cell Lines

Laine Marrah, University of Virginia School of Medicine, Department of Pathology Robert Cornelison, Ph.D., University of Virginia School of Medicine, Department of Pathology Hui Li, Ph.D., University of Virginia School of Medicine, Department of Pathology


Poster # 8


The Li lab has discovered AVIL, a gene encoding an actin-binding protein called advillin that influences cytoskeletal function and can drive several aggressive cancers. The lab overall is interested in learning more about how AVIL works on several levels, as it is a promising potential gene to target in cancer treatments. One mechanism of interest through which AVIL could cause cancer is double minutes (DMs), a DNA structure also known as extrachromosomal circular DNA. DMs exist outside of the typical regulatory elements in the chromosomal DNA and so can produce an excess of protein and drive irregular cell processes such as premature division. Computationally predicting the presence and location of DMs in cancer cells requires the creation of several input files that contain information about the cell line's DNA sequence, structural variants, and regions with copy number variation, all integrated with the use of DMFinder software. This analysis was optimized and run at a large scale using the UVA Rivanna high-performance computing system. Overall, we have predicted the presence of DMs from chromosome 12 (where AVIL is located) for over 300 cell lines from the Cancer Cell Line Encyclopedia; nearly every whole-genome sequencing sample available. Of these cell lines, about 25% were predicted to have at least one DM, and 5 were predicted to contain AVIL within a DM. The cell lines with predicted AVIL originate from breast cancer, endometrial cancer, gastric cancer, glioblastoma, and rhabdomyosarcoma. AVIL has been identified as a bona fide oncogene in glioblastoma and rhabdomyosarcoma and correlates with worse clinical outcomes in both. The predicted results for both of these cancers are promising and support that DMs may lead to AVIL overexpression. This could in turn be dysregulating cytoskeletal function and resulting in cancer.

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