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 detecti...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.CASE SUMMARY 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 nextgeneration 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 thatEGFR-targeted therapies be tried in such future cases.CONCLUSIONThe expanded applications of the cfDNA assay may open a new horizon intreatment of patients with advanced gastric cancer.展开更多
文摘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.CASE SUMMARY 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 nextgeneration 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 thatEGFR-targeted therapies be tried in such future cases.CONCLUSIONThe expanded applications of the cfDNA assay may open a new horizon intreatment of patients with advanced gastric cancer.
