Genomic Amplification and Functional Dependency of the Gamma Actin Gene ACTG1 in Uterine Cancer

Sarcomere and cytoskeleton genes, or actomyosin genes, regulate cell biology including mechanical stress, cell motility, and cell division. While actomyosin genes are recurrently dysregulated in cancers, their oncogenic roles have not been examined in a lineage-specific fashion. In this report, we investigated dysregulation of nine sarcomeric and cytoskeletal genes across 20 cancer lineages. We found that uterine cancers harbored the highest frequencies of amplification and overexpression of the gamma actin gene, . Each of the four subtypes of uterine cancers, mixed endometrial carcinomas, serous carcinomas, endometroid carcinomas, and carcinosarcomas harbored between 5~20% of gene amplification or overexpression. Clinically, patients with gains had a poor prognosis. gains showed transcriptional patterns that reflect activation of oncogenic signals, repressed response to innate immunity, or immunotherapy. Functionally, the CRISPR-CAS9 gene deletion of had the most robust and consistent effects in uterine cancer cells relative to 20 other lineages. Overall, we propose that regulates the fitness of uterine cancer cells by modulating cell-intrinsic properties and the tumor microenvironment. In summary, the functions relative to other actomyosin genes support the notion that it is a potential biomarker and a target gene in uterine cancer precision therapies.