Issues

Romero and colleagues identified recurrent inactivating deletions within MYC-associated factor X (MAX) in small cell lung cancer (SCLC) cell lines and tumors that were mutually exclusive with MYC amplification, inactivation of MAX dimerization protein (MGA), and mutations in BRG1 (also known as SMARCA4), which encodes an ATPase subunit of the SWI/SNF chromatin remodeling complex, suggesting that these genetic alterations drive SCLC through disruption of a common pathway. Indeed, BRG1 directly regulated MAX expression, and MAX upregulated MYC target genes in a BRG1-dependent manner. Moreover, BRG1 depletion selectively inhibited the growth of MAX-deficient SCLC cells, suggesting that a synthetic lethal relationship exists between these two proteins and raising the possibility that BRG1 may be a therapeutic target in SCLC. For details, please see the article by Romero and colleagues on page 292.