High Incidence of Null-Type Mutations of the <i>TP</i>53 Gene in Japanese Patients with Head and Neck Squamous Cell Carcinoma

Abstract

Objective: Molecular targeting therapy has not been generally established in head and neck squamous cell carcinoma (HNSCC) except for cetuximab treatment for targeting epidermal growth factor receptor ( EGFR ). We analyzed alterations of the TP 53, KRAS 2, and EGFR genes in Japanese HNSCC to identify subpopulations of tumors potentially susceptible or not susceptible to specific therapy based on their genetic alterations. Materials and Methods: A total of 56 Japanese subjects were included in this study. Genomic DNA of exons 5 - 9 of the TP 53, exons 1 and 2 of the KRAS 2, exons 19 - 22 of the EGFR , and their flanking sequences were amplified by polymerase chain reaction (PCR) followed by direct sequencing. Splicing variants of EGFR were examined by reverse transcription (RT)-PCR. Results: Mutations of the TP 53 and KRAS genes were detected in 25 (45%) and 2 (4%) of 56 HNSCC cases, respectively, while neither mutation nor splicing variant of EGFR was observed. The TP 53 mutation did not correlate with clinical stages or primary sites of the tumors. The patterns of nucleotide substitutions specific to HNSCC were not observed. However, the incidence of null-type mutations of the TP 53, which cannot be detected as abnormal by conventional immunohistochemical (IHC) studies, was significantly higher (10/25; 40%) than that of HNSCC reported in other countries. Conclusion: Frequent TP 53 mutations, especially null-type mutations, but infrequent or no alterations of the KRAS and EGFR suggest that the sequencing analysis of the TP 53 mutation rather than IHC analysis of p53 provides a potentially useful marker to predict the response of HNSCC to chemotherapy or radiotherapy.