Published online Apr 26, 2021. doi: 10.12998/wjcc.v9.i12.2884
Peer-review started: December 4, 2020
First decision: January 24, 2021
Revised: February 2, 2021
Accepted: March 3, 2021
Article in press: March 3, 2021
Published online: April 26, 2021
Processing time: 132 Days and 1.1 Hours
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.
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.
The expanded applications of the cfDNA assay may open a new horizon in treatment of patients with advanced gastric cancer.
Core Tip: In recent decades, increasing application of next-generation sequencing has enabled detection of molecular aberrations, including fusions. In cases where tissue is not easily obtainable, cell-free DNA is used for detecting mutations to determine the molecular profile of cancer. In this study, we report the first case of EGFR-SEPT14 fusion detected from next-generation sequencing analysis of cell-free DNA from a patient with advanced gastric cancer. We suggest expanded applications of the cell-free DNA assay regardless of cancer type, which may open a new horizon in treatment of patients with advanced gastric cancer.