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.