LAUSR

Protein sub-units of the SWI/SNF nucleosome and chromatin remodeling complexes are frequently mutated in cancer. The ARID1A and ARID1B DNA interacting component are among these mutated proteins. Alterations in ARID1A have been reported in breast, colon, lung, kidney, pancreatic, bladder, cervical, ovarian and uterine cancers whereas ARID1B mutation is less common. Additional data suggests ARID1A mutant cancers are dependent on functional ARID1B and that targeting ARID1B may be a therapeutic strategy. However, ARID1A and 1B are often co-inactivated in aggressive un/dedifferentiated carcinomas of the ovary and endometrium suggesting tumor suppressive functions might exist not only in ARID1A but also in 1B. In this study, we examined the effects of restoring ARID1A or 1B in an undifferentiated endometrial adenocarcinoma cell line harboring inactivating mutations in both genes. ACI-98 cells derived from a stage IV undifferentiated endometrial cancer were found to lack expression of ARID1A and 1B protein. We subsequently identified two individual truncating mutations in ARID1A and 1B by genomic DNA and cDNA sequencing indicating no wild-type message was expressed. Restoration of ARID1A in ACI-98 cells using a Tet-on system revealed remarkable growth inhibition, however, ARID1B restoration showed only a moderate cell growth inhibition with cells taking on a flattened phenotype. Clones of ARID1A/1B restored cells were treated w/wo doxycycline (Dox) for 48h a time point prior to cell death or morphologic changes and protein changes catalogued using LC MS/MS. We identified 771 and 1168 differentially expressed proteins (z-score Citation Format: Yutaka Shoji, Kumiko Kato-Shoji, Kelly A. Conrads, Rusheeswar Challa, Brian L. Hood, Nicholas W. Bateman, Thomas P. Conrads, John I. Risinger. ARID1A and ARID1B dependent proteomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 214. doi:10.1158/1538-7445.AM2017-214