Clinical and molecular characteristics of kinase domain duplications across diverse cancer types in the Chinese population. (3rd November 2022)

• Record Type: Journal Article
• Authors: Lai, Xiaojing; Yu, Ruoying; Ou, Qiuxiang; Bao, Hua; Wu, Xue; Shao, Yang; Li, Yang; Zhang, Ying; Ding, Qingqing
• Is Part Of: Cancer medicine. Volume 12:Number 5(2023)
• Page Start: 6009
• Page End: 6015
• Publication Date: 2022-11-03
• Subjects: EGFR amplification -- kinase domain duplication -- targeted sequencing -- TP53 gene alterations; 616.994005
• DOI: 10.1002/cam4.5325
• Languages: English
• ISSNs: 2045-7634

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. Abstract : Intact kinase domain duplications were observed at a ratio of 0.1%.The identified KDDs included 55 EGFR KDDs (exons 18–25, exons 17–25), 4 MET KDDs (exons 15–21, exons 12–21), 2 BRAF KDD (exons 10–19, exons 10–18), 1 RET KDD (exons 11–20), 1 FLT3 KDD (exons 6–23), 1 FGFR1 KDD (exons 8–18), and 1 FGFR2 KDD (exons 10–17).