Diffuse-type Gastric Carcinoma, a subtype of gastric carcinoma, is one of the most malignant cancers worldwide as well as in Japan. Genome Science Division (Prof. Hiroyuki Aburatani, Miwako Kakiuchi, Hiroki Ueda, Kengo Goto, Akimasa Hayashi, Shogo Yamamoto, and Kenji Tatsuno), in collaboration with TMDU Department of Genomic Pathology (Prof. Shumpei Ishikawa, Alumni of Genome Science Division), performed exome sequencing for clinical Diffuse-type Gastric Carcinoma, and identified frequent gain-of-function mutations of RHOA gene. Structural and functional analyses were done also with Forerunner Pharma Research Co., Ltd (Takashi Nishizawa and Shinichi Funahashi). RHOA is associated with cell movement and cell growth, and our analyses showed that newly identified mutant RHOA works in a gain-of-function manner. Diffuse-type Gastric Carcinoma cannot be included for therapeutic applications of any known molecular targeted drugs available so far. Our discovery provides us with a potential new therapeutic target against Diffuse-type Gastric Carcinoma. These results have been published in Nature Genetics (11th May online publication).
Miwako Kakiuchi, Takashi Nishizawa, Hiroki Ueda, Kengo Gotoh, Atsushi Tanaka, Akimasa Hayashi, Shogo Yamamoto, Kenji Tatsuno, Hiroto Katoh, Yoshiaki Watanabe, Takashi Ichimura, Tetsuo Ushiku, Shinichi Funahashi, Keisuke Tateishi, Ikuo Wada, Nobuyuki Shimizu, Sachiyo Nomura, Kazuhiko Koike, Yasuyuki Seto, Masashi Fukayama, Hiroyuki Aburatani, & Shumpei Ishikawa
“Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma”
Nature Genetics, 11th May, advanced online publication
Nature Genetics website