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, CWM (2014) ARID1B is a specific vulnerability in ARID1A-mutant cancers. NATURE MEDICINE. pp. 251-254.

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 ARID14-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

Item Type:	Article
Additional Information:	NIBR author: Jagani, Z institute: NIBR contributor address: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA, Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA, Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA USA ; Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA, Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA ; Broad Inst Harvard & MIT, Boston, MA USA, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA ; Broad Inst Harvard & MIT, Boston, MA USA ; Broad Inst Harvard & MIT, Boston, MA USA, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA ; Novartis Inst Biomed Res, Cambridge, MA USA ; Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA ; Broad Inst Harvard & MIT, Boston, MA USA, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA ; Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA, Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA, Broad Inst Harvard & MIT, Boston, MA USA, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA charles_roberts@dfci.harvard.edu; Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA; Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA; Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA; Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA USA; Roberts, CWM; Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/22623