sion, peritumoral enhancement, and other imaging features have been reported as predictors in HCC for MVI or posthepatectomy recurrence HCC [5][6][7]. However, independent validation of these features has not yet been performed, and these features are not yet applied widely.The Liver Imaging Reporting and Data System (LI-RADS) [8] was developed to standardized terminology, interpretation, and reporting of imaging for HCC diagnosis. The system addresses the full spectrum of liver lesions and pseudolesions with a 5-point scale reflecting the relative likelihood of HCC, from LR-1 (definitely benign) to LR-5 ( definitely HCC). LI-RADS also assigns category LR-M to observations considered probably or definitely malignant but lacking criteria specific for HCC and a separate category (LR-TIV

3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:976-987.

4 Technical Efficacy: Stage 5 J. MAGN. RESON. IMAGING 2018.

No abstract

ARID1A is a key mammalian SWI/SNF complex subunit that is mutated in 5% to 11% of lung cancers. Although recent studies have elucidated the mechanism underlying dysregulation of the switch/sucrose non-fermentable (SWI/SNF) complexes in cancers, the significance of ARID1A loss and its implications in lung cancers remain poorly defined. This study investigates how ARID1A loss affects initiation and progression of lung cancer. In genetically engineered mouse models bearing mutant Kras and a deficient Trp53 allele (KP), ARID1A loss (KPA) promoted lung tumorigenesis. Analysis of the transcriptome profiles of KP and KPA tumors suggested enhanced glycolysis following ARID1A loss, and expression of the glycolytic regulators Pgam1, pyruvate kinase M (Pkm), and Pgk1 was significantly increased in ARID1A-deficient lung tumors. Furthermore, ARID1A loss increased chromatin accessibility and enhanced hypoxia-inducible factor-1α (HIF1α) binding to the promoter regions of Pgam1, Pkm, and Pgk1. Loss of ARID1A in lung adenocarcinoma also resulted in loss of histone deacetylase 1 (HDAC1) recruitment, increasing acetylation of histone-4 lysine at the promoters of Pgam1, Pkm, and Pgk1, and subsequently enhancing BRD4-driven transcription of these genes. Metabolic analyses confirmed that glycolysis is enhanced in ARID1A-deficient tumors, and genetic or pharmacologic inhibition of glycolysis inhibited lung tumorigenesis in KPA mice. Treatment with the small molecule bromodomain and extraterminal protein (BET) inhibitor JQ1 compromised both initiation and progression of ARID1A-deficient lung adenocarcinoma. ARID1A negatively correlated with glycolysis-related genes in human lung adenocarcinoma. Overall, ARID1A loss leads to metabolic reprogramming that supports tumorigenesis but also confers a therapeutic vulnerability that could be harnessed to improve the treatment of ARID1A-deficient lung cancer. Significance: This study links ARID1A loss with enhanced glycolysis in lung cancer and demonstrates the preclinical efficacy of BET inhibitor therapy as a strategy to combat tumor growth.