title: Assessment of DDR2, BRAF, EGFR and KRAS mutations as therapeutic targets in non-adenocarcinoma lung cancer patients.
abstract: Molecular-targeted therapy has not been established in non-adenocarcinoma lung cancer (non-AdLC), as no targets that affect the clinical efficacy of molecular-targeted drugs have yet been identified. In this study, we investigated the frequency of genetic variations in discoidin domain receptor 2 (DDR2), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) in non-AdLC patients, in order to evaluate the possibility of genetic mutations in these genes being used as therapeutic targets for the treatment of patients with non-AdLC. For this purpose, we enrolled 150 non-AdLC patients who had undergone surgery at the Gunma University Hospital between December, 2003 and December, 2012. Genetic mutations in the EGFR, KRAS, DDR2 and BRAF genes were detected by a sequencing method or probe assay using DNA derived from cancer tissues. No somatic mutations in DDR2 or BRAF were detected in non-AdLC patients. Conversely, genetic mutations in EGFR exon 19 were found in 3 squamous cell carcinoma (SCC) and 3 adenosquamous carcinoma patients, whereas KRAS codon 12 mutations were also found in 3 SCC patients and 1 large-cell neuroendocrine carcinoma patient. EGFR and KRAS mutations were mutually exclusive. This study indicated that, although DDR2 and BRAF mutations may only rarely be used as therapeutic targets, EGFR and KRAS mutations may represent candidate therapeutic targets, at least in the non-AdLC patients investigated.
authors: Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan ; Department of Pharmacy, Gunma University Hospital, Maebashi, Gunma 371-8511, Japan.
authors: Hideaki
authors: H
authors: Yashima
authors: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors: Kimihiro
authors: K
authors: Shimizu
authors: Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan ; Department of Pharmacy, Gunma University Hospital, Maebashi, Gunma 371-8511, Japan.
authors: Takuya
authors: T
authors: Araki
authors: Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan ; Department of Pharmacy, Gunma University Hospital, Maebashi, Gunma 371-8511, Japan ; Center for Medical Education, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors: Tohru
authors: T
authors: Aomori
authors: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors: Yoichi
authors: Y
authors: Ohtaki
authors: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors: Toshiteru
authors: T
authors: Nagashima
authors: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors: Yasuaki
authors: Y
authors: Enokida
authors: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors: Jun
authors: J
authors: Atsumi
authors: Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan ; Department of Pharmacy, Gunma University Hospital, Maebashi, Gunma 371-8511, Japan.
authors: Tomonori
authors: T
authors: Nakamura
authors: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors: Izumi
authors: I
authors: Takeyoshi
authors: Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan ; Department of Pharmacy, Gunma University Hospital, Maebashi, Gunma 371-8511, Japan.
authors: Koujirou
authors: K
authors: Yamamoto
keywords: biomarker; discoidin domain receptor 2; epidermal growth factor receptor; lung cancer; molecular-targeted therapy; non-adenocarcinoma lung cancer; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; v-raf murine sarcoma viral oncogene homolog B1