Spectrum of acquired KRAS mutations in driver mutation-positive non-small cell lung cancer


Joshua Reuss, Nishant Gandhi, Phillip Walker, Jorge Nieva, Jean Bustamante Alvarez, Jennifer Carlisle, Aakash Desai, Ari Vanderwalde, Patrick Ma, Stephen Liu


  • With the emergence of effective therapies targeting specific KRAS mutations (mt), identifying these unique KRAS mts in NSCLC has become increasingly relevant.
  • Acquired KRAS mutations are a known resistance mechanism in driver mutation-positive (DM+) NSCLC.
  • The incidence and diversity of these acquired alterations and whether they differ from those observed in de novo KRAS mt NSCLC is unknown.
  • We aimed to characterize the distribution of KRAS mt between acquired and de novo KRAS mt NSCLC, as well as the distribution of unique KRAS mt by driver mutation.


  • While the distribution of unique KRAS mutations did not differ significantly between DN and ACQ subgroups, acquired KRAS mutations at varying frequencies were seen across DM+ NSCLC subsets.
  • The functional and immunological significance of these mutations, and their impact on clinical outcomes, warrants further investigation.
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