Catalog of 5' fusion partners in RET+ NSCLC Circa 2020

Abstract

Since the discovery of RET fusion-positive (RET+) NSCLC around late 2011 to early 2012, clinical trials of multikinase inhibitors and highly potent and selective RET tyrosine kinase inhibitors have indicated that RET fusion is an actionable oncogenic driver in NSCLC. There seems to be a differential response to multikinase inhibitors depending on the fusion partner (KIF5B-RET versus non-KIF5B-RET); thus, knowledge of the fusion partners in RET+ NSCLC is important. To date, we identified 48 unique fusion partners in RET from published literature and congress proceedings. Two of the novel fusion partners (CCNYL2 and TRIM24) were identified in RET fusions that emerged as resistant to EGFR tyrosine kinase inhibitors. In addition, multiple intergenic rearrangements were identified.

Keywords: 5′ fusion partners; NSCLC; Pralsetinib; RET; Selpercatinib; Whole-transcriptome sequencing.