Conces, Madison L.Hancock, Bradley A.Atale, RutujaSolzak, Jeffrey P.Bunting, KarenCorvelo, AndreField, LorenBadve, SunilLiu, JianyunBrutkiewicz, Randy R.Loehrer, Patrick J.Radovich, Milan2023-01-202023-01-202021Conces, M. L., Hancock, B. A., Atale, R., Solzak, J. P., Bunting, K., Corvelo, A., Field, L., Badve, S., Liu, J., Brutkiewicz, R. R., Loehrer, P. J., & Radovich, M. (2021). Whole-Genome Sequencing to Identify the Genetic Etiology of a Spontaneous Thymoma Mouse Model. Journal of Cancer Research and Cellular Therapeutics (JCRCT), 5(1). https://www.auctoresonline.org/article/whole-genome-sequencing-to-identify-the-genetic-etiology-of-a-spontaneous-thymoma-mouse-model26401053https://hdl.handle.net/1805/30987Background: A mouse model for thymoma was previously created serendipitously by the random introduction of a transgene consisting of a mouse α-cardiac promoter, a constitutively active human transforming growth factor-β, and a simian virus 40 integration sequence into C3HeB/FeJ mice. Previous data demonstrated that the likely cause of thymomas in the thymoma mouse model was due to insertional mutagenesis by the transgene. At the time, fluorescence in situ hybridization was used to localize the transgene to the short arm of chromosome 2 (Chr2qF2-G region). In this exploratory study, we aimed to identify the exact insertion site of the transgene as this could provide clues to the genetic causation of thymomas in humans. Materials and Methods: To identify the insertion site of the transgene, germline DNA from the thymoma mouse model was sequenced using low-pass, fragment-library, whole genome sequencing. Long-insert mate pair whole genome sequencing was employed to traverse the repetitive regions of the mouse’s genome and identify the integration site. Results: The transgene was found to be integrated into a repetitive area of the mouse genome, specifically on Chr2qF1 within the intron of the FAM227B gene. Tandem integration of the transgene was observed with enumeration of an estimated 30 copies. Initial results suggested that a nearby gene, fibroblast growth factor 7 (Fgf7), could be affected by the gene insertion. Conclusions: Whole genome sequencing of this thymoma mouse model identified the region of tandem integration of a transgene on Chr2qF1 that may have potential translational implications in helping to understand the genomic etiology of thymoma in humans.en-USAttribution 4.0 Internationalthymomamouse modelgenomicsviral vectorArticle