Leventakos Konstantinos, Kipp Benjamin R, Rumilla Kandelaria M, Winters Jennifer L, Yi Eunhee S, Mansfield Aaron S
Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
J Thorac Oncol. 2016 Oct;11(10):1798-801. doi: 10.1016/j.jtho.2016.05.007. Epub 2016 May 20.
Epidermal growth factor receptor gene (EGFR) mutations are relatively common oncogenic drivers in non-small cell lung cancer (NSCLC). The outcomes of patients who present with less common EGFR mutations or more than one EGFR mutation are uncertain. We reviewed our experience with the S768I mutation of exon 20 of EGFR to provide insight into the clinical significance of this mutation.
We used a natural language search program to search our electronic medical record system and every EGFR mutation analysis of patients with NSCLC treated at Mayo Clinic that was performed in our Department of Molecular Genetics to identify patients with EGFR S768I mutation. Relevant clinical and laboratory data were abstracted for selected cases, including evaluation of response after treatment with tyrosine kinase inhibitors.
A total of 1527 patients with NSCLC who underwent EGFR testing were reviewed. The S768I mutation was present in nine patients (0.59%), four of whom were female. Only three had an isolated S768I mutation, four had a concurrent G719 mutation, and two had a concurrent L858R mutation. Among patients with stage IV disease treated with erlotinib (n = 4), one had an isolated S768I mutation and three had additional mutations (two patients with G719 and one patient with L858R). The tumor response to erlotinib of patients with stage IV disease was highly variable (progression-free survival ranged from 3 to 30 months and overall survival ranged from 5 to more than 51 months).
S768I mutations in exon 20 of the EGFR gene are rare and are typically seen in conjunction with sensitizing EGFR mutations. Because of this mutation's rarity and the variability of responses of treated cases, its exact prognostic and predictive role is not fully understood. In our experience, S768I mutations in isolation do not necessarily confer sensitivity to erlotinib, but in conjunction with sensitizing EGFR mutations, S768I mutations do not restrict efficacy.
表皮生长因子受体基因（EGFR）突变是非小细胞肺癌（NSCLC）中相对常见的致癌驱动因素。具有少见EGFR突变或一种以上EGFR突变的患者的预后尚不确定。我们回顾了我们对EGFR第20外显子S768I突变的经验，以深入了解该突变的临床意义。
我们使用自然语言搜索程序搜索我们的电子病历系统以及在梅奥诊所接受治疗且在我们分子遗传学部门进行的每例NSCLC患者的EGFR突变分析，以识别具有EGFR S768I突变的患者。为选定病例提取相关临床和实验室数据，包括酪氨酸激酶抑制剂治疗后的反应评估。
共回顾了1527例接受EGFR检测的NSCLC患者。9例患者（0.59%）存在S768I突变，其中4例为女性。仅3例有孤立的S768I突变，4例同时存在G719突变，2例同时存在L858R突变。在接受厄洛替尼治疗的IV期疾病患者中（n = 4），1例有孤立的S768I突变，3例有其他突变（2例有G719突变，1例有L858R突变）。IV期疾病患者对厄洛替尼的肿瘤反应差异很大（无进展生存期为3至30个月，总生存期为5至超过51个月）。
EGFR基因第20外显子的S768I突变罕见，通常与敏感的EGFR突变同时出现。由于该突变罕见且治疗病例反应多变，其确切的预后和预测作用尚未完全明确。根据我们的经验，孤立的S768I突变不一定赋予对厄洛替尼的敏感性，但与敏感的EGFR突变同时存在时，S768I突变并不限制疗效。
