December 7-11, 2019, Walter E. Washington Convention Center, Washington, DC
Visit us at Booth 518, join us at our Tech Talk and view our poster.
Tech Talk: Monday, December 9, 2019, 1:00-1:45 p.m., Theater 1, Exhibit Hall A
Refreshments will be served.
Space is limited.
Genetic Profiling and Functional Screening for Drug Target and Biomarker Discovery
Efficient tools to enable drug target and biomarker discovery: a brief introduction to Cellecta technologies, Paul Diehl, Ph.D., Cellecta Chief Operating Officer, Mountain View, CA
ARID1A determines luminal identity and therapeutic response in estrogen receptor-positive breast cancer, Guotai Xu, Ph.D., Scaltriti Lab, Memorial Sloan Kettering Cancer Center, New York, NY
Mutations in ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, are the most common somatic alteration of the SWI/SNF complex in estrogen receptor positive (ER+) breast cancer. We identified that ARID1A inactivating mutations are present at a high frequency in advanced endocrine resistant ER+ breast cancer. An epigenome CRISPR/CAS9 knockout screen identified ARID1A as the top candidate whose loss determines resistance to the ER degrader fulvestrant. ARID1A knockout cells were found to be less responsive to endocrine therapy compared to cells with intact ARID1A in vitro and in vivo. Patients harboring alterations of ARID1A were also associated with shorter duration of response to selective ER degraders (SERDs). Mechanistically, ARID1A disruption in ER+ breast cancer cells led to widespread changes in chromatin accessibility converging on loss of activity of master transcription factors (TFs) that regulate gene expression programs critical for luminal lineage identity. Global transcriptome profiling of ARID1A knockout cell lines and patient samples harboring ARID1A inactivating mutations revealed an enrichment for basal-like gene expression signatures. The state of increased cellular plasticity of luminal cells upon ARID1A inactivation is enabled by loss of ARID1A-dependent SWI/SNF complex targeting to genomic sites of the major luminal-lineage determining transcription factors including ER, FOXA1, and GATA3. We also show that ARID1A regulates genome-wide ER-FOXA1 chromatin interactions and ER-dependent transcription. Altogether, we uncover a critical role for ARID1A in the determination of breast luminal cell identity and endocrine therapeutic response in ER+ breast cancer.
Poster # 1593: Tuesday, December 10, 2019, 12:00-1:30 p.m., Learning Center/Exhibit Hall
Clonal Analysis, Genetic Screening and Expression Profiling at a Single-Cell Level, Paul Diehl, Ph.D., Chief Operating Officer, Cellecta
We hope you can join us at our Tech Talk at 1:00 p.m. on Monday, December 9 in Theatre 1, Exhibit Hall A at ASCB|EMBO. Space is limited. Refreshments will be served.
We look forward to meeting you at Booth 518.