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

It is well known that a number of head and neck carcinomas are associated with HRAS mutations, and that several cancers with RAS mutations, such as lung cancer, have a poor prognosis. In this study, we evaluated the frequency of HRAS mutations in head and neck carcinomas and characterized the clinical and cell biological features of carcinomas with HRAS mutations. HRAS 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 HRAS 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. HRAS knockdown with siRNA suppressed the in vitro migration ability of HRAS mutation-positive cells but not that of HRAS mutation-negative cells. In conclusion, a positive HRAS mutation could be an indicator of distant metastasis and poor prognosis, as well as a potential therapeutic target.