In addition, cluster 1 included genes like DEPDC1B and HMMR that have known roles in both TME remodeling as well as CIN associated functions.44–48 Overall, our identification of cluster 1 genes indicates that a punctuated burst of expressional changes occurs simultaneously in both CIN and TME remodeling genes very early in tumor development. Here, DEPDC1B is linked to cervical squamous intraepithelial neoplasia.