To examine the effects of γ-rays on genomic instability and cancer-driver mutations, we monitored the immortalization process of wild-type mouse embryonic fibroblast cells (WT MEFs) after irradiation (1 or 10 Gy at 909 mGy/min) at early passage (P3) because these cells usually immortalize with chromosomal instability (CIN) (Atsumi et al., 2011; Ichijima et al., 2010) and mutations in the ARF/p53 pathway (Matheu et al., 2007; Osawa et al., 2013). The gene discussed is CDKN2A; the disease is cervical squamous intraepithelial neoplasia.