Cbl mutations (mt) as important mediators of oncogenic RTK signaling in NSCLC


Rebecca Feldman, Ari M. Vanderwalde, Stephen V. Liu, Martin Frederik Dietrich, Shirish M. Gadgeel, Wolfgang Michael Korn, Jorge J. Nieva, Alexander I. Spira, Edward S. Kim

Background – Casitas B-lineage lymphoma (CBL)

  • An E3 ubiquitin ligase that negatively regulates a wide range of RTKs including many drivers of NSCLC
  • Uncoupling CBL from its regulatory activities has oncogenic effects and its characterization in a large clinical data set is warranted.


  • CBL mts occurred in ~5% of a large cohort of NSCLC, 1.4% are LOF
  • CBL mts are not mutually exclusive events with oncogenic drivers, some patterns for co-occurrence
  • CBL LOF mts were found in the de-novo and post-treatment settings -> Role in acquired and pre-existing genomic landscape that facilitate bypass signaling upon therapeutic insult?
  • Future work includes – impact of CBL LOF on response to treatment with TKIs and further characterization of other CBL mts

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