Genomic assays for Epstein-Barr virus-positive gastric adenocarcinoma.

A small set of gastric adenocarcinomas (9%) harbor Epstein–Barr virus (EBV) DNA within malignant cells, and the virus is not an innocent bystander but rather is intimately linked to pathogenesis and tumor maintenance. Evidence comes from unique genomic features of host DNA, mRNA, microRNA and CpG methylation profiles as revealed by recent comprehensive genomic analysis by The Cancer Genome Atlas Network. Their data show that gastric cancer is not one disease but rather comprises four major classes: EBV-positive, microsatellite instability (MSI), genomically stable and chromosome instability. The EBV-positive class has even more marked CpG methylation than does the MSI class, and viral cancers have a unique pattern of methylation linked to the downregulation of CDKN2A (p16) but not MLH1. EBV-positive cancers often have mutated PIK3CA and ARID1A and an amplified 9p24.1 locus linked to overexpression of JAK2, CD274 (PD-L1) and PDCD1LG2 (PD-L2). Multiple noncoding viral RNAs are highly expressed. Patients who fail standard therapy may qualify for enrollment in clinical trials targeting cancer-related human gene pathways or promoting destruction of infected cells through lytic induction of EBV genes. Genomic tests such as the GastroGenus Gastric Cancer Classifier are available to identify actionable variants in formalin-fixed cancer tissue of affected patients.

一小部分胃腺癌（9%）在恶性细胞内含有爱泼斯坦 - 巴尔病毒（EBV）DNA，且该病毒并非无辜的旁观者，而是与发病机制和肿瘤维持密切相关。癌症基因组图谱网络近期进行的全面基因组分析揭示了宿主DNA、mRNA、微小RNA和CpG甲基化图谱的独特基因组特征，从而提供了相关证据。他们的数据表明，胃癌并非一种疾病，而是包含四大类：EBV阳性、微卫星不稳定（MSI）、基因组稳定和染色体不稳定。EBV阳性类型的CpG甲基化程度甚至比MSI类型更显著，并且病毒性癌症具有一种独特的甲基化模式，这种模式与CDKN2A（p16）的下调有关，但与MLH1无关。EBV阳性癌症通常有PIK3CA和ARID1A突变，以及一个与JAK2、CD274（PD - L1）和PDCD1LG2（PD - L2）过度表达相关的9p24.1位点扩增。多种非编码病毒RNA高度表达。标准治疗失败的患者可能有资格参加针对癌症相关人类基因通路的临床试验，或通过诱导EBV基因裂解来促进受感染细胞的破坏。诸如GastroGenus胃癌分类器等基因组检测可用于识别受影响患者的福尔马林固定癌症组织中的可操作变异。