Department of Thoracic Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Department of Neurosurgery, Second Affiliated Hospital of Air Force Military Medical University, Xi'an, China.
World J Surg Oncol. 2024 Jul 25;22(1):194. doi: 10.1186/s12957-024-03463-w.
Epidermal growth factor receptor (EGFR) fusions are rare but potentially actionable oncogenic drivers across multiple solid tumors. However, the distribution and molecular characteristics of EGFR fusions in Chinese patients with solid malignancies have not been explored.
Panel-based next-generation sequencing (NGS) data of 35,023 patients with various types of solid tumors was collected and analyzed from the Simcere Diagnostics (Nanjing, China) database. A 9563-patient cohort was derived from The Cancer Genome Atlas (TCGA) to explore the relationship between EGFR fusion status and overall survival (OS).
In this study, prevalence of functional EGFR fusions was 0.303% (106/35,023) in total across solid tumors, which occur more commonly in gastroesophageal junction cancer (1/61, 1.613%), followed by medulloblastoma (1/66, 1.515%) and glioma (33/2409, 1.370%). Analysis showed a prevalence for fusion partners in different tumor types. The top 3 co-mutant genes with EGFR fusion were TP53 (mutation frequency, MF: 65%), BRCA2 (MF: 43%), and ALK (MF: 41%). Furthermore, patients in the EGFR fusion group had a significantly shorter OS than those in the non-EGFR fusion group (p < 0.0001) in the TCGA cohort, suggesting that EGFR fusion might be a high-risk factor for poor prognosis.
Our study is the first retrospective analysis of EGFR fusions in a large-scale solid tumor population, which may provide a reference for future EGFR-TKI clinical trials with EGFR fusions.
表皮生长因子受体（EGFR）融合是多种实体瘤中罕见但潜在可治疗的致癌驱动因素。然而，在中国实体恶性肿瘤患者中，EGFR 融合的分布和分子特征尚未得到探索。
从中国南京的思路迪诊断（Simcere Diagnostics）数据库中收集并分析了来自 35023 例各种类型实体肿瘤患者的基于面板的下一代测序（NGS）数据。从癌症基因组图谱（TCGA）中提取了一个包含 9563 例患者的队列，以探讨 EGFR 融合状态与总生存期（OS）之间的关系。
本研究中，在所有实体肿瘤中，功能性 EGFR 融合的总体发生率为 0.303%（106/35023），在胃食管交界癌（1/61，1.613%）中更为常见，其次是髓母细胞瘤（1/66，1.515%）和神经胶质瘤（33/2409，1.370%）。分析显示了不同肿瘤类型中融合伙伴的流行情况。与 EGFR 融合的前 3 个共突变基因是 TP53（突变频率，MF：65%）、BRCA2（MF：43%）和 ALK（MF：41%）。此外，在 TCGA 队列中，EGFR 融合组患者的 OS 明显短于非 EGFR 融合组（p<0.0001），这表明 EGFR 融合可能是预后不良的高危因素。
本研究是对大规模实体肿瘤人群中 EGFR 融合的首次回顾性分析，可为未来 EGFR-TKI 临床试验中针对 EGFR 融合的研究提供参考。
