LAUSR

Gastric cancer is one of most common malignant tumors. Although chemotherapy can improve the survival of gastric cancer, the benefit is limited because most cancer cells eventually become irresponsive to chemotherapeutic drugs. To investigate mechanism of resistance to chemotherapy, we performed whole-exome sequencing (WES) on resistant tumor and paired normal samples from 14 patients received adjuvant chemotherapy. We found that 3 patients had novel somatic mutations in mitogen-activated protein kinase kinase kinase 10 (MAP3K10), an upstream kinase of mitogen activated protein kinase (MAPK). MAP3K10R304C, MAP3K10H211R, or MAP3K10A30E were detected each patient, respectively. The survival rate was higher and apoptosis rate was smaller in the cells expressing each MAP3K10 mutations compared with parental controls and cells expressing wild-type MAP3K10, when treated with cisplatin or 5-FU. Moreover, cells expressing each MAP3K10 mutations exhibited higher levels of phosphorylated MEK1/2 and p38MAPK at baseline and when treated with cisplatin or 5-FU than wild-type AGS or MKN45 cells or those expressing wild-type MAP3K10. In summary, MAP3K10R304C, MAP3K10H211R, and MAP3K10A30E MAP3K10 confer resistance to cisplatin or 5-FU via activation of MAPK pathway in gastric cancer cells. Thus, somatic MAP3K10 mutations could be a potential biomarker for predicting resistance to chemotherapy for gastric cancer patients Citation Format: Chae Hwa Kwon, Sun Jin Lee, Yuri Choi, Do Youn Park. MAP3K10 mutation as a biomarker for predicting response to chemotherapy in gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3365.