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

Authors:

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.

Conclusions

  • 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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