Bi Xiaojun, Song Pengyu, Wang Chengye, Zhang Xuefei, Liu Changhong
Department of Thoracic Surgery, The Second Hospital of Dalian Medical University, Dalian, China.
Transl Cancer Res. 2022 May;11(5):1423-1428. doi: 10.21037/tcr-21-2604.
Epidermal growth factor receptor () gene is one of the most common driver genes for non-small cell lung cancer (NSCLC). The PIONEER study showed that 51.4% of unselected Asian patients with advanced lung adenocarcinoma have -sensitive mutations. mutations mainly occur in the first four [18-21] exons of the intracellular tyrosine kinase (TK) region. At present, there are more than 30 types of mutations in the TK region, including exon 19 deletion mutation (19Del) and exon 21 L858R mutation (L858R) which are the most common types of sensitive mutations, accounting for more than 90% of all mutations. About 10% of NSCLC patients with mutations are rare mutation types, including exon 18 point mutation (G719X), exon 20 point mutation (S768I), exon 19 point mutation (L747S), exon 21 point mutation (L833V), etc. About 1% of NSCLC patients have primary double mutations of .
In this present study, we identified a 59-year-old female patient with no smoking history had double mutations in exon 20 R776S mutation and exon 21 L858R mutation by next-generation sequencing (NGS).
This observation may explore a new mechanism study for EGFR-TKIs and provide a new direction for clinical treatment of NSCLC.
表皮生长因子受体（EGFR）基因是非小细胞肺癌（NSCLC）最常见的驱动基因之一。先锋研究表明，51.4%未经过筛选的亚洲晚期肺腺癌患者存在EGFR敏感突变。EGFR突变主要发生在细胞内酪氨酸激酶（TK）区域的前四个外显子[18 - 21]。目前，TK区域存在30多种突变类型，其中外显子19缺失突变（19Del）和外显子21 L858R突变（L858R）是最常见的敏感突变类型，占所有EGFR突变的90%以上。约10%携带EGFR突变的NSCLC患者为罕见突变类型，包括外显子18点突变（G719X）、外显子20点突变（S768I）、外显子19点突变（L747S）、外显子21点突变（L833V）等。约1%的NSCLC患者存在EGFR原发性双突变。
在本研究中，我们通过二代测序（NGS）鉴定出一名59岁无吸烟史的女性患者，其EGFR外显子20存在R776S突变和外显子21存在L858R突变。
这一观察结果可能为EGFR - TKIs的新机制研究探索方向，并为NSCLC的临床治疗提供新的方向。
