Clinical and molecular characteristics of kinase domain duplications across diverse cancer types in the Chinese population

Abstract

Abstract Background Kinase domain duplications (KDDs) have recently been recognized as oncogenic mutations and possible association with drug resistance in cancers. Method Here, targeted sequencing was performed with the tumor tissue and/or plasma from 65 cancer patients with KDDs. Result Intact KDDs were identified in approximately 0.1% of the total population across multiple cancer types. EGFR KDD was first identified in colorectal cancer and breast cancer, whereas FGFR2 KDD was first identified in gastric cancer. Tumors with EGFR KDD displayed lower concurrent TP53 gene alterations (p = 0.03) and slightly higher chromosome instability (p = 0.27) compared to tumors with non‐EGFR‐KDDs. Immune pathway analysis further revealed the enrichment of the cytokine receptors pathway (93%) in the KDD carriers. Hyperprogression‐related gene mutations were identified in four cases. Conclusion Collectively, our data revealed the genomic features of KDD alterations in a multi‐cancer cohort, providing more information for the potential treatment application in the KDD carriers.

Keywords

• EGFR amplification
• kinase domain duplication
• targeted sequencing
• TP53 gene alterations