Comprehensive profiling of EGFR mutation subtypes reveals genomic-clinical associations in non-small-cell lung cancer patients on first-generation EGFR inhibitors

• DOI: 10.1016/j.neo.2023.100888
• Publication Date: 2023-02-16T23:34:03Z
• Authors: Yongkang Bai; Xiang Liu; Limin Zheng; Song Wang; Junli Zhang; Shi Xiong; Pengfei Zhang; Zichen Jiao; Gefei Zhao; Chu Zhou; Jiaohui Pang; Yang Xu; Qiuxiang Ou; Yuan Mao; Louqian Zhang
• Keywords: Original article; Common EGFR; Lung Neoplasms; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Genomics; Uncommon EGFR; NSCLC; 3. Good health; ErbB Receptors; 03 medical and health sciences; 0302 clinical medicine; EGFR-TKI; Carcinoma, Non-Small-Cell Lung; Mutation; Humans; Protein Kinase Inhibitors; RC254-282

Common sensitizing mutations in epidermal growth factor receptor (cEGFR), including exon 19 deletions (19-Del) and 21 L858R substitution, are associated with high sensitivity to EGFR-TKIs NSCLC patients. The treatment for patients uncommon EGFR (uEGFR) remains a subject of debate due heterogeneity responses. In this manuscript, the targeted next-generation sequencing (NGS) data large cohort EGFR-mutated was assessed elucidate genomic profiles tumors carrying cEGFR or uEGFR mutations. results showed that were more likely harbor co-occurring genetic alterations Hippo pathway higher TMB compared cEGFR-positive Smoking-related found significantly enriched uEGFR-positive Subgroup analyses performed identify potential prognostic biomarkers harboring various subtype L858R-positive co-existing ARID2 had shorter progression-free survival (PFS) than those who L858R- 19-Del-positive but ARID2-negative (median: 2.3 vs. 12.0 8.0 months, P = 0.038). Furthermore, mutational profiles, such as top frequently mutated genes signatures different. Our study analyzed landscape mutations, revealing specific characteristics might explain poor prognosis first-generation EGFR-TKIs.