The DpY motif within the exon 14 juxta-membrane domain of the MET receptor gene is a critical regulatory site on the MET gene, specifically, where Cbl docks to mediate negative regulation. Splicing alterations that delete this residue, known as exon 14 skipping mutations (ex14sk mt), lead to prolonged MET protein stability and oncogenic signaling. Specific mt at the Y1021 (aka 1003) residue (actual Cbl docking site) are thought to lead to similar effects as ex14sk, but due to their rarity, their role in NSCLC is unknown.
Retrospective review of molecular profiles for non-ex14sk mt that include/surround the DpY motif (Y1021) in MET. Numbers updated since ASCO abstract submision. Two NGS platforms were included: MiSeq (2014-2017; n = 2865) and NextSeq (2017-2019; n = 7963). Immunohistochemistry (IHC) of cMET (SP44) and co-occurring alterations (EGFR, KRAS, ALK, ROS, etc.) were also reviewed.