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

International Journal of Molecular Sciences
Camden RichterDanuta Szczesna-Cordary

Abstract

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, ACTG1. Each of the four subtypes of uterine cancers, mixed endometrial carcinomas, serous carcinomas, endometroid carcinomas, and carcinosarcomas harbored between 5~20% of ACTG1 gene amplification or overexpression. Clinically, patients with ACTG1 gains had a poor prognosis. ACTG1 gains showed transcriptional patterns that reflect activation of oncogenic signals, repressed response to innate immunity, or immunotherapy. Functionally, the CRISPR-CAS9 gene deletion of ACTG1 had the most robust and consistent effects in uterine cancer cells relative to 20 other lineages. Overall, we propose that ACTG1 regulates the fitness of uterine cancer cells by modulating cell-intrinsic properties and the tumor microenvironment. In su...Continue Reading

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Clinical Trials Mentioned

NCT01897571
NCT02220842
NCT03874455
NCT03348631
NCT03884101
NCT03517449

Software Mentioned

TCIA
OncoPrint
GSEA
cBioPortal
Gene Set Enrichment Analysis ( GSEA )
Depmap

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