Genome-wide epigenetic landscape of lung adenocarcinoma links HOXB9 DNA methylation to intrinsic EGFR-TKI resistance and heterogeneous responses
Journal
JCO Precision Oncology
Journal Volume
5
Pages
418-431
Date Issued
2021
Author(s)
Liu, Chia-Hsin
Cheng, Chiou-Ling
Yang, Tsung-Ying
Chen, Kun-Chieh
Hsu, Kuo-Hsuan
Tseng, Jeng-Sen
Chang, Gee-Chen
Li, Ker-Chau
Abstract
PURPOSE: -activating mutations. However, a significant subset of targeted patients fail to respond. Unlike acquired resistance (AR), intrinsic resistance (IR) remains poorly understood. We investigated whether epigenomic factors contribute to patient-to-patient heterogeneity in the EGFR-TKI response and aimed to characterize the IR subpopulation that obtains no benefit from EGFR-TKIs. PATIENTS AND METHODS: -activating mutations. RESULTS: = .019). CONCLUSION: Our data suggest that homeobox DNA methylation could be a novel tumor cellular state that can aid the precise categorization of tumor heterogeneity in the study of IR to EGFR-TKIs. We identified, for the first time, an epigenomic factor that can potentially complement DNA mutation status in discriminating patients with lung adenocarcinoma who are less likely to benefit from EGFR-TKI treatment, thereby leading to improved patient management in precision medicine.
Publisher
American Society of Clinical Oncology
Type
journal article