染色锁蛋白3（CBX3）的过度表达是癌症中常见的事件，促进了癌细胞的增殖，并在大量人类癌症中代表了不良预后的标志。在本文中，我们描述了一系列人类癌症携带了CBX3基因与EGFR或RAC1的共同扩增，这导致CBX3、EGFR和RAC1的mRNA和蛋白水平都显著增加。我们还揭示了CBX3、RAC1和EGFR基因产物的同时过表达与预后较差的相关性，与CBX3、RAC1和EGFR分别单独上调时相比。此外，我们还发现CBX3与EGFR或RAC1之间的低度扩增与高度扩增同时存在会导致患者的寿命缩短。最后，我们发现CBX3和RAC1/EGFR在模式生物黑腹果蝇中存在遗传互作关系，这表明这些基因的同时过度表达以及高度或低度的拷贝数变异的共存并非偶然，可能反映了进化上保守的功能关系。© 2023 年 细胞死亡分化协会（ADMC）。

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.© 2023. Cell Death Differentiation Association (ADMC).