Background: Osimertinib is a novel and irreversible epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) targeting EGFR  sensitive mutations and EGFR  exon20 p.T790M mutation, which demonstrated superior progression-free survival (PFS) and overall survival (OS).
Case Presentation: We report a patient with lung adenocarcinoma harboring EGFR  exon 19 deletion mutant treatment with icotinib. After 6 months, she developed EGFR  exon20 p.T790M and then the patient received osimertinib treatment. A novel MYH9  (exon41)-RET  (exon12) fusion and EGFR  exon20 p.T790M loss were identified using plasma circulation tumor DNA (ctDNA) after osimertinib treatment, which led to rapid progression after osimertinib five months and suggested a potential resistance mechanism.
Conclusion: Our findings expanded the spectrum of RET  arrangement types and provided the basis for this hypothesis: acquired RET  rearrangement and EGFR  exon20 p.T790M loss potentially serve an additional resistance mechanism to osimertinib in EGFR -mutated non-small-cell lung cancer (NSCLC).
Keywords: MYH9-RET  fusion, EGFR  exon20 p.T790M loss, lung adenocarcinoma, acquired resistance, osimertinib