Co-amplification of CBX3 with EGFR or RAC1 in human cancers corroborated by a conserved genetic interaction among the genes

Chromobox Protein 3 (CBX3) overexpression is a common event occurring in cancer, promotes cancer cell proliferation and represents a poor prognosis marker in a plethora of human cancers. Here we describe that a wide spectrum of human cancers harbors a co-amplification of CBX3 gene with either EGFR or RAC1, which yields a statistically significant increase of both mRNA and protein levels of CBX3, EGFR and RAC1. We also reveal that the simultaneous overexpression of CBX3, RAC1 and EGFR gene products correlates with a worse prognosis compared to the condition when CBX3, RAC1 and EGFR are singularly upregulated. Furthermore, we also show that a co-occurrence of low-grade amplification, in addition to high-grade amplification, between CBX3 and EGFR or RAC1 is associated with a reduced patient lifespan. Finally, we find that CBX3 and RAC1/EGFR genetically interact in the model organism Drosophila melanogaster, suggesting that the simultaneous overexpression as well as well the co-occurrence of high- or low-grade copy number alterations in these genes is not accidental and could reflect evolutionarily conserved functional relationships.

Automated summary

CBX3 overexpression is common in cancer and promotes cancer cell proliferation, serving as a poor prognosis marker in various types of human cancers. Co-amplification of CBX3 gene with either EGFR or RAC1 results in increased levels of CBX3, EGFR, and RAC1. Simultaneous overexpression of CBX3, RAC1, and EGFR is associated with worse prognosis compared to singular upregulation of these genes. Co-occurrence of low-grade and high-grade amplification between CBX3 and EGFR or RAC1 is linked to reduced patient lifespan. Genetic interactions between CBX3 and RAC1/EGFR are observed in Drosophila melanogaster, suggesting evolutionarily conserved functional relationships.