Dai Limeng, Su Xuejiao, Lu Lin, Lv Donglai
Department of Medical Genetics.
Fifth Brigade 16th Team, College of Basic Medical Science, Army Medical University (Third Military Medical University), Chongqing.
Medicine (Baltimore). 2018 Dec;97(51):e13809. doi: 10.1097/MD.0000000000013809.
Mutation p.A289V involving extracellular region of epidermal growth factor receptor (EGFR) exon 7 has not yet been reported in nonsmall cell lung cancer (NSCLC). Studies have shown p.A289V mutation responding to tyrosine kinase inhibitors (TKIs) in glioblastoma cell lines suggesting the point mutation as a potential therapeutic target. However, sufficient evidence of the effect of TKI treatment on the p.A289V mutation involved in NSCLC is not available.
An 80-year-old nonsmoker male with lung mass was suffering from severe bone pain.
Needle biopsy and positron emitted tomography/computed tomography were performed. The patient was diagnosed with advanced NSCLC adenocarcinoma with bone and lymphatic metastasis. Next-generation sequencing of circulating tumor DNA was performed, which identified a p.A289V mutation in the EGFR gene of the patient.
Our patient refused to receive chemotherapy and tried Icotinib treatment.
Our patient had a partial response to Icotinib after treatment for 5 months during the therapeutic trial by TKIs. The patient showed adverse symptoms of mild diarrhea and rash (Common Terminology Criteria for Adverse Events grade 1) during the treatment.
In this case, Icotinib prevented completion of the signal transduction cascade of p.A289V mutant in NSCLC. Our finding may expand the EGFR mutation spectrum for TKI treatment in NSCLC. However, the finding needs to be confirmed at a larger scale with NSCLC in Chinese and other populations.
表皮生长因子受体(EGFR)外显子7细胞外区域的p.A289V突变在非小细胞肺癌(NSCLC)中尚未见报道。研究表明,胶质母细胞瘤细胞系中p.A289V突变对酪氨酸激酶抑制剂(TKIs)有反应,提示该点突变是一个潜在的治疗靶点。然而,关于TKI治疗对NSCLC中涉及的p.A289V突变影响的充分证据尚不明确。
一名80岁的不吸烟男性,肺部有肿块,伴有严重骨痛。
进行了穿刺活检和正电子发射断层扫描/计算机断层扫描。患者被诊断为晚期NSCLC腺癌伴骨和淋巴结转移。对循环肿瘤DNA进行了二代测序,结果显示患者的EGFR基因存在p.A289V突变。
我们的患者拒绝接受化疗,尝试使用埃克替尼治疗。
在TKIs治疗试验中,患者接受埃克替尼治疗5个月后出现部分缓解。治疗期间,患者出现轻度腹泻和皮疹的不良症状(不良事件通用术语标准1级)。
在本病例中,埃克替尼阻止了NSCLC中p.A289V突变体信号转导级联的完成。我们的发现可能会扩大NSCLC中TKI治疗的EGFR突变谱。然而,这一发现需要在中国和其他人群的更大规模NSCLC研究中得到证实。