原句：Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.© 2022. The Author(s). 原文中文翻译：胃原发性厚壁癌（GLP）是一种具有不良存活率的胃癌亚型。GLP的全面分子特征和假定的治疗靶点仍未确定。我们对10对肿瘤正常组织进行了全外显子组测序（WES）和全转录组测序（WTS）。10个肿瘤样本全部为GLP，宏观上包含胃壁的100％。通过比较TCGA数据，得出GLP中最常见的突变基因和过度表达基因。我们的结果表明，GLP具有独特的基因组和转录组特征，Hippo通路功能失调可能是GLP发展的关键步骤。在GLP中，鉴定了6个基因（包括AOX1、ANKRD36C、CPXM1、PTPN14、RPAP1和DCDC1）为高突变率基因。作为先前被鉴定为胃癌驱动基因的MUC6在GLP中具有高突变率（20％）。我们GLP队列中的20％患者具有CDH1突变，而没有RHOA突变。GLP表现出高的免疫缺陷和低的AMPK通路活性。我们的WTS结果显示，GLP中与PI3K-AKT通路相关的三个基因（PIK3R2、AKT3和IGF1）明显上调。使用免疫组织化学（IHC）鉴定了两个基因，IGF2BP3和MUC16，在弥漫型相关的胃癌细胞系中具有特异性表达，并且其沉默抑制了PI3K-AKT通路活性。我们提供了GLP的第一个综合基因组和转录组资料，可以促进其诊断、预后和治疗。©2022年。作者（s）。

Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined.We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP.Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity.We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.© 2022. The Author(s).