Mutations in SWI SNF subunits have context-specific prognostic effects in driver subsets of NSCLC


Benjamin Herzberg, Nishant Gandhi, Brian Henick, Joanne Xiu, Ari Vanderwalde, Joshua Reuss, Carla Concepcion-Crisol


  • In this largest-ever retrospective cohort of NSCLC patients with SWI/SNF mutations, SMARCA4 mutation and to a lesser extent PBRM1 mutation are the only SWI/SNF alterations associated with worse survival.
  • SMARCA4 mutation is overrepresented in KRASmut NSCLC and in NSCLC without a known classical strong driver (such as EGFR mutation, ALK fusion) • SMARCA4 mutation is associated with particularly short survival in KRASmt tumors indicating a potential cooperation of KRASmt and SMARCA4mt to drive poor prognosis in NSCLC.
  • These effects are robust to control for KEAP1, and STK11 status.
  • The cooperativity with KRAS may explain why different datasets have shown varying effects and in particular differing effects of immunotherapy in SMARCA4 mutant NSCLC.
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