Increased radiosensitivity is associated with p53 mutations in cell lines derived from oral cavity carcinoma.

Abstract

The curability of oral cavity carcinomas, as well as of other head and neck cancers, varies remarkably especially in more advanced disease. Radiotherapy and surgery, including large operations, are currently combined, but as new radiotherapy regimens are being introduced, the need for predictive assays has increased in order to plan a suitable individual treatment for the patient. Variations in intrinsic radiation sensitivity of cancer cells cannot alone explain differences in therapy outcome, and thus additional predictive variables have to be searched. Mutations in the p53 tumor suppressor gene are found in most head and neck tumors, which has led us to study the possible association between these mutations and radiation sensitivity. We analyzed 16 cell lines from oral cavity carcinomas and found a remarkable variation in radiosensitivity (AUC 1.7-2.3 Gy and SF2 0.31-0.51). The p53 gene was mutated in 11/16 cell lines, and these cells were also significantly more sensitive than those with wildtype p53 (AUC 1.9 +/- 0.2 Gy and 2.3 +/- 0.2 Gy, respectively, p = 0.023). Structural alterations in the p53 gene were also observed in three of the relatively resistant cell lines, which indicates that not all mutations are critical in this respect.