胃腺癌（GAC）是一种致命的疾病，其特点是基因组和临床的多样性。通过整合先前建立的8个GAC亚型的基因组签名，我们确定了6个临床和分子上明显不同的基因组共识亚型（CGS）。CGS1预后最差，具有非常高的干细胞特征和高的IGF1表达，但基因组变异较低。CGS2富集了典型上皮基因表达。CGS3和CGS4具有高的拷贝数变化和低的免疫反应性。然而，CGS3和CGS4之间的区别在于CGS3具有高的HER2活性，而CGS4具有高的SALL4和KRAS活性。CGS5具有高突变负担和中等免疫反应性，这是微卫星不稳定性肿瘤的特征。大多数CGS6肿瘤阳性表达EB病毒，并且显示极高的甲基化水平和高的免疫反应性。在对基因组和蛋白质组学数据进行系统分析后，我们估计了每个共识亚型对标准和实验性治疗的潜在反应率，如放射治疗、靶向治疗和免疫治疗。有趣的是，由于其高基础水平的铁死亡，CGS3与化学放射治疗的效益显著相关。此外，我们还确定了每个共识亚型的潜在治疗靶点。因此，共识亚型产生了一个强大的分类，并为基于亚型的定制干预提供了额外的特征描述。© 2023. BioMed Central Ltd., part of Springer Nature.

Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions.© 2023. BioMed Central Ltd., part of Springer Nature.