Kim Boyeon, Kim Yoonjung, Park Inho, Cho Jae Yong, Lee Kyung-A
Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea.
Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, South Korea.
World J Clin Cases. 2021 Apr 26;9(12):2884-2889. doi: 10.12998/wjcc.v9.i12.2884.
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 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 frameshift mutation (NM_000038.5:c.6579del, p.V2194fs) with variant allele frequency of 0.5%, an amplification with a copy number of 17.3, and an fusion with variant allele frequency of 45.3%. The site of the fusion was exon 24 of fused to exon 10 of The fusion was in-frame and considered to be protooncogenic. Although the patient refused to continue therapy, we suggest that -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.
胃癌是全球第五大最常被诊断出的癌症，也是癌症相关死亡的第三大常见原因。近几十年来，下一代测序技术的应用日益广泛，能够检测包括融合在内的分子畸变。在难以获取组织的情况下，游离DNA（cfDNA）被用于检测突变以确定癌症的分子特征。在此，我们报告一例通过cfDNA分析在一名胃癌患者中检测到罕见融合的病例。
一名49岁女性于2019年7月被诊断为晚期胃癌，接受了卡培他滨治疗，随后接受雷莫西尤单抗和紫杉醇联合化疗，但出现了腹水。治疗改为纳武单抗，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。治疗中断，并立即对cfDNA进行下一代测序评估。从cfDNA中分析了所有基因组变异，包括融合。从患者的cfDNA中检测到以下体细胞改变：一个移码突变（NM_000038.5:c.6579del，p.V2194fs），变异等位基因频率为0.5%，一个拷贝数为17.3的扩增，以及一个变异等位基因频率为45.3%的融合。融合位点是 的第24外显子与 的第10外显子融合。该融合为框内融合，被认为是原癌基因性的。尽管患者拒绝继续治疗，但我们建议在未来此类病例中尝试 靶向治疗。
cfDNA检测的扩展应用可能为晚期胃癌患者的治疗开辟新的前景。
