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Squamous cell carcinomas (SCCs) are supposed to develop through the multistep process that involves activation of proto-oncogenes and/or inactivation of tumor suppressor genes in the human epidermis. To elucidate the multistep process, we screened mutations in H-Ras, p53, PTEN, and the INK4a locus in 21 SCCs by meansof PCR-SSCP analysis. One, 3, and 7 SCCs were detected mutations in H-Ras, INK4a, and p53, respectively. No mutation was detected in PTEN in any SCC. Nine SCCs in total were shown to have mutations at least in one gene. Among them, we detected both mutations of H-Ras and INK4a in one SCC, and both mutations of p53 and INK4a in another SCC. In particular, activation of H-Ras and inactivation of both of p16INK4a and p14ARF were supposed in the former SCC. This finding indicates the possibility that the combination of mutations might contribute to the cacinogenesis in the SCC. [Skin Cancer (Japan) 2001; 16: 353-356]

Mutations of cancer-related genes in squamous cell carcinomas of the human skin.