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ARID1B is a specific vulnerability in ARID1A-mutant cancers.
|Publication Type||Journal Article|
|Authors||Helming, KC, Wang X., Wilson BG, Vazquez F., Haswell JR, Manchester HE, Kim Y., Kryukov GV, Ghandi M., Aguirre AJ, Jagani Z., Wang Z., Garraway LA, Hahn WC, and Roberts CW|
|Abstract||Recent studies have revealed that ARID1A, encoding AT-rich interactive domain 1A (SWI-like), is frequently mutated across a variety of human cancers and also has bona fide tumor suppressor properties. Consequently, identification of vulnerabilities conferred by ARID1A mutation would have major relevance for human cancer. Here, using a broad screening approach, we identify ARID1B, an ARID1A homolog whose gene product is mutually exclusive with ARID1A in SWI/SNF complexes, as the number 1 gene preferentially required for the survival of ARID1A-mutant cancer cell lines. We show that loss of ARID1B in ARID1A-deficient backgrounds destabilizes SWI/SNF and impairs proliferation in both cancer cells and primary cells. We also find that ARID1A and ARID1B are frequently co-mutated in cancer but that ARID1A-deficient cancers retain at least one functional ARID1B allele. These results suggest that loss of ARID1A and ARID1B alleles cooperatively promotes cancer formation but also results in a unique functional dependence. The results further identify ARID1B as a potential therapeutic target for ARID1A-mutant cancers.|
|Year of Publication||2014|
|Date Published (YYYY/MM/DD)||2014/03/01|