HRAS Mutations in Head and Neck Carcinomas in Japanese Patients: Clinical Significance, Prognosis, and Therapeutic Potential

It is well known that a number of head and neck carcinomas are associated with <i>HRAS</i> mutations, and that several cancers with <i>RAS</i> mutations, such as lung cancer, have a poor prognosis. In this study, we evaluated the frequency of <i>HRAS</i> mutations in head and neck carcinomas and characterized the clinical and cell biological features of carcinomas with <i>HRAS</i> mutations. <i>HRAS</i> mutations at codons 12, 13, and 61, mutational hot spots, were evaluated in tissue specimens obtained from 119 Japanese patients treated at our institution. DNA was successfully extracted from 100 specimens, and sequencing was completed. An <i>HRAS</i> mutation was found in 8 (8.0%) cases: 5 (6.1%) out of 82 HNSCCs and 3 (16.7%) out of 18 salivary gland carcinomas. Mutations were found at codons 12 and 61, while none were found at codon 13, which differs from previous reports. The mutation-positive cases had a relatively poor prognosis, consistent with previous reports, and were more frequently accompanied by distant metastasis. <i>HRAS</i> knockdown with siRNA suppressed the in vitro migration ability of <i>HRAS</i> mutation-positive cells but not that of <i>HRAS</i> mutation-negative cells. In conclusion, a positive <i>HRAS</i> mutation could be an indicator of distant metastasis and poor prognosis, as well as a potential therapeutic target.