Mutation analysis of the EGFR pathway genes, EGFR, RAS, PIK3CA, BRAF, and AKT1, in salivary gland adenoid cystic carcinoma
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Kosuke Saida1,2,*, Takayuki Murase1,*, Mayuko Ito1, Kana Fujii1, Hisashi Takino1, Ayako Masaki1, Daisuke Kawakita3, Kei Ijichi3, Yuichiro Tada4, Kimihide Kusafuka5, Yoshiyuki Iida6, Tetsuro Onitsuka6, Yasushi Yatabe7, Nobuhiro Hanai8, Yasuhisa Hasegawa8, Hitomi Shinomiya9, Ken-Ichi Nibu9, Kazuo Shimozato2 and Hiroshi Inagaki1
1Department of Pathology and Molecular Diagnostics, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
2Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan
3Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
4Department of Head and Neck Oncology and Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan
5Pathology Division, Shizuoka Cancer Center, Nagaizumi, Shizuoka, Japan
6Department of Head and Neck Surgery, Shizuoka Cancer Center, Nagaizumi, Shizuoka, Japan
7Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan
8Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
9Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
*These authors contributed equally to this work
Hiroshi Inagaki, email: [email protected]
Keywords: adenoid cystic carcinoma; salivary gland; EGFR pathway mutations; RAS mutations; SNaPshot assay
Received: June 16, 2017 Accepted: February 24, 2018 Published: March 30, 2018
Adenoid cystic carcinoma (AdCC), one of the most common salivary gland carcinomas, usually has a fatal outcome. Epidermal growth factor receptor (EGFR) pathway gene mutations are important in predicting a patient’s prognosis and estimating the efficacy of molecular therapy targeting the EGFR pathway. In this study of salivary gland AdCC (SAdCC), we looked for gene mutations in EGFR, RAS family (KRAS, HRAS, and NRAS), PIK3CA, BRAF, and AKT1, using a highly sensitive single-base extension multiplex assay, SNaPshot. Out of 70 cases, EGFR pathway missense mutations were found in 13 (18.6%): RAS mutations in 10 (14.3%), EGFR in one (1.4%), and PIK3CA in 5 (7.1%). None of the cases showed an EGFR deletion by direct sequencing. Concurrent gene mutations were found in three cases (4.3%). EGFR pathway mutations were significantly associated with a shorter disease-free (p = 0.011) and overall survival (p = 0.049) and RAS mutations were as well; (p = 0.010) and (p = 0.024), respectively. The gene fusion status as determined by a FISH assay had no significant association with mutations of the genes involved in the EGFR pathway. In conclusion, EGFR pathway mutations, especially RAS mutations, may be frequent in SAdCC, and associated with a poor prognosis for the patient.
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