Moisseev Alexey, Albert Eugene, Lubarsky Dan, Schroeder David, Clark Jeffrey
Institute for personalized medicine, I.M. Sechenov First Moscow State Medical University, 119048 Moscow, Russia.
Quantida, Inc., Newton, MA 02466, USA.
Biomedicines. 2020 Mar 23;8(3):67. doi: 10.3390/biomedicines8030067.
Gastric cancer is globally the fifth leading cause of cancer death. We present a case report describing the unique genomic characteristics of an Epstein-Barr virus-negative gastric cancer with esophageal invasion and regional lymph node metastasis. Genomic tests were performed first with the stomach biopsy using platforms FoundationOne, OncoDNA, and Oncopanel at Dana Farber Institute. Following neoadjuvant chemotherapy, residual tumor was resected and the stomach and esophageal residual tumor samples were compared with the initial biopsy by whole exome sequencing and molecular pathway analysis platform Oncobox. Copy number variation profiling perfectly matched the whole exome sequencing results. A moderate agreement was seen between the diagnostic platforms in finding mutations in the initial biopsy. Final data indicate somatic activating mutation Q546K in gene, somatic frameshifts in and genes, stop-gain in , and a few somatic mutations of unknown significance. RNA sequencing analysis revealed upregulated expressions of and genes and strongly differential regulation of several molecular pathways linked with the mutations identified. According to test results, the patient received immunotherapy with anti-PD1 therapy and is now free of disease for 2 years. Our data suggest that matched tumor and normal tissue analyses have a considerable advantage over tumor biopsy-only genomic tests in stomach cancer.
胃癌是全球第五大致癌死亡原因。我们报告一例病例，描述了一例具有食管侵犯和区域淋巴结转移的爱泼斯坦-巴尔病毒阴性胃癌的独特基因组特征。首先在达纳-法伯癌症研究所使用FoundationOne、OncoDNA和Oncopanel平台对胃活检组织进行基因组检测。新辅助化疗后，切除残余肿瘤，并通过全外显子测序和分子通路分析平台Oncobox将胃和食管残余肿瘤样本与初始活检样本进行比较。拷贝数变异分析与全外显子测序结果完全匹配。在初始活检中发现突变时，各诊断平台之间存在中度一致性。最终数据显示， 基因存在体细胞激活突变Q546K， 基因和 基因存在体细胞移码突变， 基因存在终止密码子获得突变，还有一些意义不明的体细胞突变。RNA测序分析显示 基因和 基因表达上调，并且与所鉴定突变相关的几种分子通路存在强烈的差异调节。根据检测结果，该患者接受了抗PD1免疫治疗，目前已无病生存2年。我们的数据表明，在胃癌中，肿瘤组织与正常组织的配对分析比仅进行肿瘤活检的基因组检测具有相当大的优势。
