High frequency of p53 mutations in ultraviolet radiation-induced murine skin tumors : evidence for strand bias and tumor heterogeneity

• Published in: Cancer research (Chicago, Ill.) Vol. 53; no. 13; pp. 2961 - 2964
• Main Authors: KANJILAL, S, PIERCEALL, W. E, CUMMINGS, K. K, KRIPKE, M. L, ANANTHASWAMY, H. N
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.07.1993
• Subjects: Alleles; Animal tumors. Experimental tumors; Animals; Base Sequence; Biological and medical sciences; DNA Damage; DNA, Neoplasm - genetics; DNA, Neoplasm - radiation effects; Experimental skin tumors; Female; Genes, p53 - genetics; Genes, p53 - radiation effects; Medical sciences; Mice; Mice, Inbred C3H; Molecular Sequence Data; Mutagenesis; Mutation - radiation effects; Neoplasms, Radiation-Induced - genetics; Skin Neoplasms - etiology; Skin Neoplasms - genetics; Transcription, Genetic - genetics; Transcription, Genetic - radiation effects; Tumors; Ultraviolet Rays - adverse effects; Skin disease; Nucleotide sequence; Pathogenesis; Rodentia; Exploration; Malignant tumor; Carcinogenesis; Heterogeneity; Vertebrata; Mammalia; Ultraviolet irradiation; Mouse; Animal; Skin; Mutation; Tumor suppressor gene
• ISSN: 0008-5472; 1538-7445

Exposure to UV radiation has long been associated with the development of skin cancers. To identify the molecular targets in UV carcinogenesis, we analyzed 11 UV-induced murine skin cancers for mutations in the p53 tumor suppressor gene and found a 100% incidence rate. Such a high frequency of p53 mutations is unprecedented and suggests that this gene plays an important role in the development of UV-induced skin cancers. The mutations were predominantly "UV-signature" transitions (C-->T and CC-->TT) at pyrimidine-rich sequences located on the nontranscribed strand of the gene. In addition, seven tumors harbored multiple mutant alleles of p53, providing strong evidence for tumor heterogeneity at the molecular level.