背景:胃癌是全球第五大诊断癌症,也是癌症相关死亡的第三大常见原因。近几十年来,下一代测序的越来越多的应用使得分子畸变的检测成为可能,包括融合。在组织难以获得的情况下,无细胞DNA(cfDNA)用于检测突变以鉴定癌症的分子谱。这里,我们报道了一例罕见的胃癌患者的cfDNA分析发现EGFR-SEPT14融合。
方法:2019年7月诊断为晚期胃癌的49岁女性,接受卡培他滨,然后雷莫西单抗和紫杉醇联合化疗,但发现了腹水.治疗改用了nivolumab,但在2020年5月的正电子发射断层扫描/计算机断层扫描中观察到疾病进展.停止治疗,和cfDNA下一代测序立即评估。所有基因组变异,包括融合,从cfDNA分析。从患者的cfDNA中检测到以下体细胞改变:APC移码突变(NM_000038.5:c.6579del,p.V2194fs)变异等位基因频率为0.5%,EGFR扩增,拷贝数为17.3,EGFR-SEPT14融合,变异等位基因频率为45.3%。融合位点是与SEPT14的外显子10融合的EGFR的外显子24。融合在框架内并被认为是原癌基因。虽然病人拒绝继续治疗,我们建议在未来此类病例中尝试EGFR靶向治疗.
结论:cfDNA分析的扩展应用可能为晚期胃癌患者的治疗开辟了新的视野。
BACKGROUND: Gastric cancer is the fifth most diagnosed cancer worldwide and the third most common cause of cancer-related death. In recent decades, increasing application of next-generation sequencing has enabled detection of molecular aberrations, including fusions. In cases where tissue is difficult to obtain, cell-free DNA (cfDNA) is used for detecting mutations to identify the molecular profile of cancer. Here, we report a rare
case of EGFR-SEPT14 fusion detected from cfDNA analysis in a patient with gastric cancer.
METHODS: A 49-year-old female diagnosed with advanced gastric cancer in July 2019 received capecitabine and then combination chemotherapy of ramucirumab and paclitaxel, but ascites was detected. The therapy was switched to nivolumab, but disease progression was observed on a positron emission tomography/computed tomography scan in May 2020. Therapy was discontinued, and cfDNA next-generation sequencing was immediately evaluated. All genomic variants, including fusions, were analyzed from cfDNA. The following somatic alterations were detected from the patient\'s cfDNA: an APC frameshift mutation (NM_000038.5:c.6579del, p.V2194fs) with variant allele frequency of 0.5%, an EGFR amplification with a copy number of 17.3, and an EGFR-SEPT14 fusion with variant allele frequency of 45.3%. The site of the fusion was exon 24 of EGFR fused to exon 10 of SEPT14. The fusion was in-frame and considered to be protooncogenic. Although the patient refused to continue therapy, we suggest that EGFR-targeted therapies be tried in such future cases.
CONCLUSIONS: The expanded applications of the cfDNA assay may open a new horizon in treatment of patients with advanced gastric cancer.