Methylation of <i>FAM110C</i> is a synthetic lethal marker for ATR/CHK1 inhibitors in pancreatic cancer.
Fengna Liu, Aiai Gao, Meiying Zhang, Yazhuo Li, Fan Zhang, James G. Herman, Mingzhou Guo
Abstract
Background and objectives: ) is a cell fate-related gene and its function in cancer remains unclear. Methods: Seven cell lines, 34 cases of intraductal papillary mucinous neoplasm (IPMN), 15 cases of mucinous cystic neoplasm (MCN) and 284 cases of PDAC samples were employed. Methylation-specific PCR, western blot, CRISPR knockout, immunoprecipitation and a xenograft mouse model were used in this study. Results: expression sensitizes PDAC cells to VE-822 (an ATR inhibitor) and MK-8776 (a CHK1 inhibitor). Conclusion: methylation is a potential diagnostic and prognostic marker in PDAC, and its epigenetic silencing sensitizes PDAC cells to ATR/CHK1 inhibitors.