Abstract 139: Novel gastric cancer cell lines established from diffuse type gastric cancer patients for potential subgroup-specific therapy
Authors: Kim Tae Soo , Park Kyu Hyun , Kwon Woo Sun , Lee Won Suk , Jeong In Hye , Kang Sun Kyoung , Kim Hyun Myong , Rha Sun Young , Chung Hyun Cheol 
Published: July 2016

In vitro culture system is a long-standing useful tool in the study of cell biology for developing new therapeutic modalities and discovering new anti-cancer drugs. Therefore establishment and characterization of cell lines are very important in vitro study. However, establishment of GC patients derived cell lines are very challenging, especially with diffuse type which has different biology and worse prognosis from intestinal type.

Yonsei Cancer Center (YCC) has been consistently worked to build human cancer cell lines, and resulting in over 30 novel cancer cell lines from metastatic gastric cancer patients. Most of YCC GC cell lines were established by primary culture of peritoneal fluid from metastatic gastric cancer patients. Interestingly, YCC-16 cells were isolated from the peripheral blood of gastric cancer patients. 20 cells were established from diffuse type GC, and 21 cells were from signet ring cell type.

In this study, we evaluated 29 YCC GC cell lines and 23 GC cell lines from other sources (ATCC, KCLB, and JCRB). For molecular characterization of 52 GC cell lines, we analyzed copy number variant (CNV), single number variant (SNV) and gene expression using whole-exome sequencing (WES) and RNA sequencing. The 7 cell lines (YCC-17, 18, 19, 20, 29, 34, 36) were compared with their germline variants of paired PBMC. Also, these cell lines were investigated expression of proteins related to cancer progression and the sensitivity of chemotherapies and diverse molecular targeted drugs/antibodies. We evaluated the tumorigenesis with soft-agar assay and invasiveness by transwell assay.

In addition to previous novel EBV infected cell line (YCCEL1/YCC-10, J Gen Virol. 2013), we observed amplification and overexpression of receptor tyrosine kinase (RTK) including HER2 (YCC-19, 32, 33, 38, 42), EGFR (YCC-11, 21), Met (YCC-31, 42), and FGFR2 (YCC-28, 30); confirming that protein was overexpression by Western blot in 20/52 (38.5%). Interestingly, amplification of RTKs was detected mutually exclusive pattern with other RTK amplification. Furthermore, RTK amplified cell lines were shown to be sensitive to target specific small molecules such as BGJ398. Also, we identified cell line specific genetic variations including ARID1A which might be the potential new targets in diffuse type GC cell lines. Then we could subgroup the cell lines based on 4 subtypes of TCGA.

In conclusion, our GC cell line bank with genomic and biological characteristics based on the clinical information, would be useful in subgroup specific target selection, drug screening and mechanism evaluation for improving GC treatment.

Citation Format: Tae Soo Kim, Kyu Hyun Park, Woo Sun Kwon, Won Suk Lee, In Hye Jeong, Sun Kyoung Kang, Hyun Myong Kim, Sun Young Rha, Hyun Cheol Chung. Novel gastric cancer cell lines established from diffuse type gastric cancer patients for potential subgroup-specific therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 139.